A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia

Last updated: February 26, 2025
Sponsor: National Cancer Institute (NCI)
Overall Status: Active - Not Recruiting

Phase

3

Condition

Leukemia

Lymphoma

Down's Syndrome

Treatment

Prednisone

Radiation Therapy

Asparaginase Erwinia chrysanthemi

Clinical Study ID

NCT03914625
NCI-2019-02187
AALL1731
U10CA180886
NCI-2019-02187
  • Ages 365-31
  • All Genders

Study Summary

This phase III trial studies how well blinatumomab works in combination with chemotherapy in treating patients with newly diagnosed, standard risk B-lymphoblastic leukemia or B-lymphoblastic lymphoma with or without Down syndrome. Monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as vincristine, dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine, mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin decreases the toxic effects of methotrexate. Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells. Giving blinatumomab and combination chemotherapy may work better than combination chemotherapy alone in treating patients with B-ALL. This trial also assigns patients into different chemotherapy treatment regimens based on risk (the chance of cancer returning after treatment). Treating patients with chemotherapy based on risk may help doctors decide which patients can best benefit from which chemotherapy treatment regimens.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • All B-ALL patients must be enrolled on APEC14B1 and consented to EligibilityScreening (Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not arequirement for B-LLy patients. B-LLy patients may directly enroll on AALL1731.

  • Age at diagnosis:

  • Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS).

  • Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS).

  • Patients must be >= 365 days and =< 31 years of age (B-LLy patients with orwithout DS).

  • B-ALL patients without DS must have an initial white blood cell count < 50,000/uL (performed within 7 days prior to enrollment).

  • B-ALL patients with DS are eligible regardless of the presenting white blood cellcount (WBC) (performed within 7 days prior to enrollment).

  • Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blastson a bone marrow (BM) aspirate;

  • OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, thediagnosis can be established by a pathologic diagnosis of B-ALL on a BM biopsy;

  • OR a complete blood count (CBC) documenting the presence of at least 1,000/uLcirculating leukemic cells;

  • OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with orwithout Down syndrome.

  • Note: For B-LLy patients with tissue available for flow cytometry, thecriterion for diagnosis should be analogous to B-ALL. For tissue processed byother means (i.e., paraffin blocks), the methodology and criteria forimmunophenotypic analysis to establish the diagnosis of B-LLy defined by thesubmitting institution will be accepted (diagnostic biopsy for B-LLy must beperformed within 14 days prior to enrollment).

  • All patients and/or their parents or legal guardians must sign a written informedconsent.

  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

Exclusion

Exclusion Criteria:

  • Patient must not have secondary ALL that developed after treatment of a priormalignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with aprior history of transient myeloproliferative disease (TMD) are not considered tohave had a prior malignancy. They would therefore be eligible whether or not the TMDwas treated with cytarabine.

  • With the exception of steroid pretreatment or the administration of intrathecalcytarabine, patients must not have received any prior cytotoxic chemotherapy foreither the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior toinitiation of protocol therapy on AALL1731.

  • For patients receiving steroid pretreatment, the following additional exclusioncriteria apply:

  • Non-DS B-ALL patients must not have received steroids for more than 24 hours inthe 2 weeks prior to diagnosis without a CBC obtained within 3 days prior toinitiation of the steroids.

  • DS and non-DS B-LLy patients must not have received > 48 hours of oral or IVsteroids within 4 weeks of diagnosis.

  • Patients who have received > 72 hours of hydroxyurea within 1 week (7 days) prior tothe start of systemic protocol therapy.

  • B-ALL patients who do not have sufficient diagnostic bone marrow submitted forAPEC14B1 diagnostic testing and who do not have a peripheral blood sample submittedcontaining > 1,000/uL circulating leukemia cells.

  • Patient must not have acute undifferentiated leukemia (AUL).

  • Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status mustbe known prior to enrollment).

  • Note: DS patients with CNS3 disease are eligible but will be assigned to theDS-High B-ALL arm. CNS status must be determined based on a sample obtainedprior to administration of any systemic or intrathecal chemotherapy, except forsteroid pretreatment.

  • Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testiculardisease are eligible but will be assigned to the DS-High B-ALL arm).

  • For LLy patients, the following additional exclusion criteria apply:

  • T-Lymphoblastic Lymphoma.

  • Morphologically unclassifiable lymphoma.

  • Absence of both B-cell and T-cell phenotype markers in a case submitted aslymphoblastic lymphoma.

  • CNS positive disease or testicular involvement.

  • M2 (5% - 25% blasts) or M3 (> 25% blasts) marrow.

  • Patients with known Charcot-Marie-Tooth disease.

  • Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL,regardless of blast immunophenotype.

  • Patients requiring radiation at diagnosis.

  • Female patients who are pregnant since fetal toxicities and teratogenic effects havebeen noted for several of the study drugs. A pregnancy test is required for femalepatients of childbearing potential.

  • Lactating females who plan to breastfeed their infants.

  • Sexually active patients of reproductive potential who have not agreed to use aneffective contraceptive method for the duration of their study participation.

Study Design

Total Participants: 6720
Treatment Group(s): 16
Primary Treatment: Prednisone
Phase: 3
Study Start date:
July 03, 2019
Estimated Completion Date:
September 30, 2027

Study Description

PRIMARY OBJECTIVES:

I. To determine in a randomized manner if the addition of 2 cycles of blinatumomab to standard therapy improves disease-free survival (DFS) in patients with standard risk (SR) B-ALL and higher risk features (SR-High), and patients with standard-risk average (SR-Avg) B-ALL who are negative for minimal residual disease (MRD) by flow cytometry but have detectable or indeterminate MRD as measured by high-throughput sequencing (HTS) at end of induction (EOI).

II. To confirm that boys in the standard-risk favorable (SR-Fav) subset of B-ALL, with or without Down syndrome (DS), will maintain a 5-year DFS of greater than 93% when treated with a standard chemotherapy regimen with a treatment duration of 2 years from the start of interim maintenance I (IM1).

SECONDARY OBJECTIVES:

I. To describe the DFS for patients with SR-Avg B-ALL who are negative for MRD measured by flow cytometry and HTS at EOI when treated with standard chemotherapy with a treatment duration of 2 years from the start of IM1, regardless of sex.

II. To describe the DFS for patients with standard-risk favorable (SR-Fav) B-ALL when treated with a standard chemotherapy regimen.

III. To determine if patients with DS-High achieve a reduction of treatment-related mortality (TRM) after replacement of intensive elements of standard chemotherapy (omission of anthracyclines in induction, omission of the second month of delayed intensification [DI]) with 3 cycles of blinatumomab.

IV. To describe the DFS characterized by the replacement of intensive elements of standard chemotherapy with 3 cycles of blinatumomab in patients with DS-High B ALL.

V. To describe the DFS for patients with localized (Murphy stage I and II) B lymphoblastic lymphoma (B-LLy) receiving standard risk B-ALL therapy.

VI. To compare the change in neurocognitive functioning, as measured by the CogState Cognitive Composite, from baseline to end-of-therapy among patients with ALL ages 4- < 10 years at the time of diagnosis between children from poor families (defined as presence of household material hardship [HMH], including either food, housing or energy insecurity) and non-poor families (absence of HMH).

VII. To describe the impact of blinatumomab on caregiver burden and patient/proxy-reported symptoms among a subset of children enrolled in the HMH and neurocognitive outcome study.

VII. To evaluate available peripheral blood (PB) samples at EOI using HTS MRD and compare the results against bone marrow (BM) results.

IX. To evaluate available end of Consolidation (EOC) BM samples using HTS in patients who were Day 29 MRD positive by flow cytometry and who have submitted EOC BM flow cytometry results.

EXPLORATORY OBJECTIVES:

I. To explore adaptive and innate immune functions and host genetic factors associated with severe infectious complications in children with DS B-ALL.

II. To explore the impact of acute lymphoblastic leukemia (ALL) and its therapy on neurocognitive, functional, and quality of life outcomes in patients with DS and ALL, as measured by caregiver (parent/legal guardian) questionnaires.

III. To define the prevalence of minimal marrow disease (MMD) in B-LLy and to correlate MMD at diagnosis with outcome in patients with B-LLy.

IV. To explore the significance of and genomic landscape of Ig clonal composition in pediatric B-ALL.

V. To explore the incidence of HTS MRD ≥ 0.01% versus (vs.) HTS MRD < 0.01% in patients with multiparameter flow cytometry defined MRD < 0.01% at end of Induction and genetically characterize those with discordance defined by the 0.01% threshold.

OUTLINE: All patients are assigned to, and complete an INDUCTION treatment regimen. Patients are then assigned to a CONSOLIDATION treatment regimen. Finally, following CONSOLIDATION, patients are either assigned or randomized to 1 of 7 arms.

NON-DS SR B-ALL INDUCTION: Patients receive cytarabine intrathecally (IT) on day 1, vincristine intravenous (IV) push over 1 minute on days 1, 8, 15, and 22, dexamethasone orally (PO) or IV twice daily (BID) on days 1-28, pegaspargase IV over 1-2 hours or intramuscularly (IM) on day 4, and methotrexate IT on days 8 and 29. CNS2 patients also receive cytarabine IT twice weekly except during weeks when days 8 and 29 methotrexate is administered. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

  • After Non-DS SR B-ALL INDUCTION, SR-Fav and SR-Avg patients complete SR CONSOLIDATION, while patients with SR-High complete high-risk (HR) CONSOLIDATION.

DS B-ALL INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV push over 1 minute on days 1, 8, 15, and 22, pegaspargase IV over 1-2 hours or IM on day 4, methotrexate IT on days 8 and 29, and leucovorin PO or IV every 6 hours for 2 doses on days 9 and 30. Additionally, patients under 10 years of age receive dexamethasone PO or IV BID on days 1-28, and patients 10 years of age or older receive prednisone or prednisolone PO or IV BID on days 1-28. CNS2 patients also receive cytarabine IT twice weekly except during weeks when days 8 and 29 IT methotrexate is administered. CNS3 patients also receive methotrexate IT on days 15 and 22, and leucovorin PO or IV every 6 hours for 2 doses on days 16 and 23. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

  • After DS B-ALL INDUCTION, patients without high risk features and MRD < 0.01 % complete SR CONSOLIDATION. Patients without high risk features and MRD >= 0.01%, OR with high risk features and any MRD complete HR CONSOLIDATION.

NON-DS B-LLy INDUCTION: Patients receive cytarabine IT on day 1 and twice weekly if CNS2, vincristine IV push over 1 minute on days 1, 8, 15, and 22, dexamethasone PO or IV BID on days 1-28, pegaspargase IV over 1-2 hours or IM on day 4, and methotrexate IT on days 8 and 29. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

  • After NON-DS B-LLy INDUCTION, all B-LLy patients then complete SR CONSOLIDATION.

DS B-LLY INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV push over 1 minute on days 1, 8, 15, and 22, pegaspargase IV over 1-2 hours or IM on day 4, methotrexate IT on days 8 and 29, and leucovorin PO or IV every 6 hours for 2 doses on days 9 and 30. Additionally, patients under 10 years of age receive dexamethasone PO or IV BID on days 1-28, and patients 10 years of age or older receive PO or IV prednisone or methylprednisolone on days 1-28. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

  • After DS B-LLy INDUCTION, patients then complete SR CONSOLIDATION.

SR CONSOLIDATION: Patients receive vincristine IV push over 1 minute on day 1, mercaptopurine PO on days 1-28, and methotrexate IT on days 1, 8, and 15. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on days 2, 9, and 16. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

  • After SR CONSOLIDATION, patients with MRD undetectable are assigned to ARM A, and patients with MRD detectable/indeterminate/unavailable are randomized to ARM A or B. Patients with SR-Fav and all B-LLy patients are assigned to treatments identical to that in ARM A.

HR CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39, vincristine IV push over 1 minute on days 15, 22, 43, and 50, mercaptopurine PO on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 , and pegaspargase IV over 1-2 hours or IM on days 15 and 43. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on days 2, 9, 16, and 23 (on days 2 and 9 only for DS CNS3 patients). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. Patients with continued clinical evidence of DS or testicular leukemia (from diagnosis through the end of Induction) undergo testicular radiation therapy over 12 fractions once daily (QD).

  • After HR CONSOLIDATION, patients are randomized to ARM C or D. DS B-ALL patients with MRD < 1% are assigned to an arm including three blocks of blinatumomab.

ARM A:

  • INTERIM MAINTENANCE I: Patients receive vincristine IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, and methotrexate IT on day 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • DELAYED INTENSIFICATION: Patients receive methotrexate IT on day 1 and 29, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV push over 1 minute on days 1, 8, and 15, doxorubicin IV push/infusion over 1-15 minutes on days 1, 8, and 15, pegaspargase IV over 1-2 hours or IM on day 4, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 29-32 and 36-39. DS patients receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 30. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • INTERIM MAINTENANCE II: Patients receive vincristine IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes undiluted or 10-15 minutes diluted on days 1, 11, 21, 31, and 41, and methotrexate IT on days 1 and 31. DS patients receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • MAINTENANCE: Non-DS patients receive methotrexate IT on day 1, vincristine IV push over 1 minute on day 1, dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. DS patients receive vincristine IV push over 1 minute on day 1, methotrexate IT on day 1, dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78, and leucovorin IV or PO on day 2 if DS. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of INTERIM MAINTENANCE I is reached in the absence of disease progression or unacceptable toxicity.

ARM B:

  • BLINATUMOMAB BLOCK I: Patients receive dexamethasone IV or PO on day 1, methotrexate IT on day 1, and blinatumomab IV continuously on days 1-28. DS patients also receive leucovorin IV or PO every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

  • INTERIM MAINTENANCE I: Patients receive vincristine IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, and methotrexate IT on day 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • BLINATUMOMAB BLOCK II: Patients receive methotrexate IT on day 1, and blinatumomab IV continuously on days 1-28. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

  • DELAYED INTENSIFICATION: Patients receive methotrexate IT on day 1 and 29, dexamethasone PO or IV on days 1-7 and 15-21, vincristine IV push over 1 minute on days 1, 8, and 15, doxorubicin IV push/infusion over 1-15 minutes on days 1, 8, and 15, pegaspargase IV over 1-2 hours or IM on day 4, cyclophosphamide IV over 30-60

  • INTERIM MAINTENANCE I: Patients receive vincristine IV push over 1 minute on days 1,&#xd; 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes&#xd; (diluted) on days 1, 11, 21, 31, and 41, and methotrexate IT on day 31. DS patients&#xd; also receive leucovorin PO or IV every 6 hours for 2 doses on day 32. Treatment&#xd; continues for 56 days in the absence of disease progression or unacceptable&#xd; toxicity.&#xd; &#xd;

  • DELAYED INTENSIFICATION: Patients receive methotrexate IT on day 1 and 29,&#xd; dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV push over 1 minute&#xd; on days 1, 8, and 15, doxorubicin IV push/infusion over 1-15 minutes on days 1, 8,&#xd; and 15, pegaspargase IV over 1-2 hours or IM on day 4, cyclophosphamide IV over&#xd; 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30&#xd; minutes or subcutaneously (SC) on days 29-32 and 36-39. DS patients receive&#xd; leucovorin PO or IV every 6 hours for 2 doses on days 2 and 30. Treatment continues&#xd; for 56 days in the absence of disease progression or unacceptable toxicity.&#xd; &#xd;

  • INTERIM MAINTENANCE II: Patients receive vincristine IV push over 1 minute on days&#xd; 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes undiluted or 10-15 minutes&#xd; diluted on days 1, 11, 21, 31, and 41, and methotrexate IT on days 1 and 31. DS&#xd; patients receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 32.&#xd; Treatment continues for 56 days in the absence of disease progression or&#xd; unacceptable toxicity.&#xd; &#xd;

  • MAINTENANCE: Non-DS patients receive methotrexate IT on day 1, vincristine IV push&#xd; over 1 minute on day 1, dexamethasone PO on days 1-5, mercaptopurine PO on days&#xd; 1-84, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. DS&#xd; patients receive vincristine IV push over 1 minute on day 1, methotrexate IT on day&#xd; 1, dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO&#xd; on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78, and leucovorin IV or PO on&#xd; day 2 if DS. Treatment repeats every 84 days until a total duration of therapy of 2&#xd; years from start of INTERIM MAINTENANCE I is reached in the absence of disease&#xd; progression or unacceptable toxicity.&#xd; &#xd;

ARM B:&#xd; &#xd;

  • BLINATUMOMAB BLOCK I: Patients receive dexamethasone IV or PO on day 1, methotrexate&#xd; IT on day 1, and blinatumomab IV continuously on days 1-28. DS patients also receive&#xd; leucovorin IV or PO every 6 hours for 2 doses on day 2. Treatment continues for 35&#xd; days in the absence of disease progression or unacceptable toxicity.&#xd; &#xd;

  • INTERIM MAINTENANCE I: Patients receive vincristine IV push over 1 minute on days 1,&#xd; 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes&#xd; (diluted) on days 1, 11, 21, 31, and 41, and methotrexate IT on day 31. DS patients&#xd; also receive leucovorin PO or IV every 6 hours for 2 doses on day 32. Treatment&#xd; continues for 56 days in the absence of disease progression or unacceptable&#xd; toxicity.&#xd; &#xd;

  • BLINATUMOMAB BLOCK II: Patients receive methotrexate IT on day 1, and blinatumomab&#xd; IV continuously on days 1-28. DS patients also receive leucovorin PO or IV every 6&#xd; hours for 2 doses on day 2. Treatment continues for 35 days in the absence of&#xd; disease progression or unacceptable toxicity.&#xd; &#xd;

  • DELAYED INTENSIFICATION: Patients receive methotrexate IT on day 1 and 29,&#xd; dexamethasone PO or IV on days 1-7 and 15-21, vincristine IV push over 1 minute on&#xd; days 1, 8, and 15, doxorubicin IV push/infusion over 1-15 minutes on days 1, 8, and&#xd; 15, pegaspargase IV over 1-2 hours or IM on day 4, cyclophosphamide IV over 30-60&#xd; minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. DS patients receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 30. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • INTERIM MAINTENANCE II: Patients receive vincristine IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, and methotrexate IT on days 1 and 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and

    1. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • MAINTENANCE: Non-DS patients receive methotrexate IT on day 1 (omit cycles 5-6), vincristine IV push over 1 minute on day 1, dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (omit day 1 when coinciding with IT methotrexate). DS patients receive methotrexate IT on day 1 (omit cycles 5-6), dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (omit day 1 when coinciding with IT methotrexate), for DS patients and leucovorin IV or PO every 6 hours for 2 doses on day 2 (omit on final 2 cycles). Treatment repeats every 84 days until a total duration of therapy of 2 years from start of INTERIM MAINTENANCE I is reached in the absence of disease progression or unacceptable toxicity.

ARM C:

  • INTERIM MAINTENANCE I: Patients receive vincristine IV push over 1 minute on days 1, 15, 29, and 43, high dose methotrexate IV on days 1, 15, 29, and 43, mercaptopurine PO on days 1-14, 15-28, 29-42, and 43-56, methotrexate IT on day 1 and 29, and leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • DELAYED INTENSIFICATION: Patients receive methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV over 1 minute on days 1, 8, 15, 43, and 50, doxorubicin IV over 1-15 minutes on days 1, 8, and 15, pegaspargase IV over 1-2 hours or IM on days 4 and 43, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • INTERIM MAINTENANCE II: Patients receive vincristine IV over 1 minute on days 1, 11, 21, 31, and 41, Capizzi style methotrexate IV over 2-5 minutes (undiluted) or over 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase IV over 1-2 hours or IM on days 2 and 22. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • MAINTENANCE: Patients receive vincristine IV over 1 minute on day 1, prednisone or prednisolone or methylprednisolone PO or IV on days 1-5, mercaptopurine PO on days 1-84, methotrexate IT on days 1 and 29 of cycles 1-2 and on day 1 of subsequent cycles, methotrexate PO on days 8, 15, 22, 29 (for cycle 3 and later only), 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of interim maintenance I is reached in the absence of disease progression or unacceptable toxicity.

ARM D:

  • BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or IV on day 1, methotrexate IT on day 1, and blinatumomab IV continuously on days 1-28. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

  • INTERIM MAINTENANCE I: Patients receive vincristine IV over 1 minute on days 1, 15, 29, and 43, high dose methotrexate IV on days 1, 15, 29, and 43, mercaptopurine PO on days 1-14, 15-28, 29-42, and 43-56, methotrexate IT on days 1 and 29, and leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • BLINATUMOMAB BLOCK II: Patients receive blinatumomab IV on days 1-28 and methotrexate IT on day 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

  • DELAYED INTENSIFICATION: Patients receive methotrexate IT on day 1, dexamethasone PO or IV on days 1-7 and 15-21, vincristine IV over 1 minute on days 1, 8, 15, 43, and 50, doxorubicin IV over 1-15 minutes on days 1, 8, and 15, pegaspargase IV over 1-2 hours or IM on days 4 and 43, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • INTERIM MAINTENANCE II: Patients receive vincristine IV over 1 minute on days 1, 11, 21, 31, and 41, Capizzi style methotrexate IV over 2-5 minutes (undiluted) or over 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase IV over 1-2 hours or IM on days 2 and 22. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • MAINTENANCE: Patients receive methotrexate IT on day 1, vincristine IV over 1 minute on day 1, prednisone, prednisolone or methylprednisolone PO or IV on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of interim maintenance I is reached in the absence of disease progression or unacceptable toxicity.

DS-HIGH B-ALL:

  • BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or IV on day 1, blinatumomab IV continuously on days 1-28, methotrexate IT on day 1 (or on day 56 of Consolidation), and leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

  • INTERIM MAINTENANCE: Patients receive vincristine IV push over 1 minute on days 1, 15, 29, and 43, intermediate dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, mercaptopurine PO on days 1-14, 15-28, 29-42, and 43-46, methotrexate IT on days 1 and 29, and leucovorin PO or IV every 6 hours for 2 doses on days 2-4, 16-18, 30-32, and 44-46. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

  • BLINATUMOMAB BLOCK II: Patients receive blinatumomab IV on days 1-28, methotrexate IT on day 1, and leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

  • DELAYED INTENSIFICATION: Patients receive vincristine IV over 1 minute on days 1, 8, and 15, doxorubicin IV over 1-15 minutes on days 1, 8, and 15, dexamethasone PO or IV on days 1-7 and 15-21, methotrexate IT on day 1, leucovorin PO or IV every 6 hours for 2 doses on day 2, and pegaspargase IV over 1-2 hours or IM on day 4. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

  • BLINATUMOMAB BLOCK III: Patients receive blinatumomab IV on days 1-28, methotrexate IT on day 1, and leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

  • MAINTENANCE: Patients receive vincristine IV push over 1 minute on day 1, prednisone, prednisolone or methylprednisolone PO or IV BID on days 1-5, mercaptopurine PO on days 1-84, methotrexate IT on day 1, methotrexate PO on days 8, 15, 22, 29 (omit day 29 for first 3 cycles for patients who do not receive cranial radiotherapy), 36, 43, 50, 57, 64, 71, and 78, and leucovorin PO on days 2 and 30 (day 30 dose is for cycles 1-3 and for patients who do not receive cranial radiotherapy). CNS3 patients receive cranial radiotherapy during first 4 weeks of cycle 1. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of interim maintenance I is reached in the absence of disease progression or unacceptable toxicity.

All B-LLy patients:

  • INTERIM MAINTENANCE I: Patients receive vincristine IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 (diluted) on days 1, 11, 21, 31, and 41, and methotrexate IT on day 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • DELAYED INTENSIFICATION: Patients receive vincristine IV push over 1 minute on days 1, 8 and 15, doxorubicin IV over 1-15 minutes on days 1, 8, and 15, dexamethasone PO or IV on days 1-7 and 15-21, methotrexate IT on days 1 and 29, pegaspargase IV over 1-2 hours or IM on day 4, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. DS patients additionally receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 30. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • INTERIM MAINTENANCE II: Patients receive vincristine IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, and methotrexate IT on days 1 and 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and

    1. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

  • MAINTENANCE: Patients receive vincristine IV push over 1 minute on day 1, dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, methotrexate IT on day 1, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of interim maintenance I is reached in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 weeks until complete blood count(CBC)/differential/platelet count recovery, then every 3 months for the first 2 years, then every 4-6 months for the 3rd year, and every 6-12 months for the 4th and 5th years.

Connect with a study center

  • John Hunter Children's Hospital

    Hunter Regional Mail Centre, New South Wales 2310
    Australia

    Site Not Available

  • The Children's Hospital at Westmead

    Westmead, New South Wales 2145
    Australia

    Site Not Available

  • Queensland Children's Hospital

    South Brisbane, Queensland 4101
    Australia

    Site Not Available

  • Women's and Children's Hospital-Adelaide

    North Adelaide, South Australia 5006
    Australia

    Site Not Available

  • Monash Medical Center-Clayton Campus

    Clayton, Victoria 3168
    Australia

    Site Not Available

  • Royal Children's Hospital

    Parkville, Victoria 3052
    Australia

    Site Not Available

  • Perth Children's Hospital

    Perth, Western Australia 6009
    Australia

    Site Not Available

  • Alberta Children's Hospital

    Calgary, Alberta T3B 6A8
    Canada

    Site Not Available

  • University of Alberta Hospital

    Edmonton, Alberta T6G 2B7
    Canada

    Site Not Available

  • British Columbia Children's Hospital

    Vancouver, British Columbia V6H 3V4
    Canada

    Site Not Available

  • CancerCare Manitoba

    Winnipeg, Manitoba R3E 0V9
    Canada

    Site Not Available

  • Janeway Child Health Centre

    Saint John's, Newfoundland and Labrador A1B 3V6
    Canada

    Site Not Available

  • IWK Health Centre

    Halifax, Nova Scotia B3K 6R8
    Canada

    Site Not Available

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario L8N 3Z5
    Canada

    Site Not Available

  • Kingston Health Sciences Centre

    Kingston, Ontario K7L 2V7
    Canada

    Site Not Available

  • Children's Hospital

    London, Ontario N6A 5W9
    Canada

    Site Not Available

  • Children's Hospital of Eastern Ontario

    Ottawa, Ontario K1H 8L1
    Canada

    Site Not Available

  • Hospital for Sick Children

    Toronto, Ontario M5G 1X8
    Canada

    Site Not Available

  • The Montreal Children's Hospital of the MUHC

    Montreal, Quebec H3H 1P3
    Canada

    Site Not Available

  • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

    Sherbrooke, Quebec J1H 5N4
    Canada

    Site Not Available

  • Jim Pattison Children's Hospital

    Saskatoon, Saskatchewan S7N 0W8
    Canada

    Site Not Available

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan S7N 4H4
    Canada

    Site Not Available

  • CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

    Quebec, G1V 4G2
    Canada

    Site Not Available

  • Centre Hospitalier Universitaire de Quebec

    Quebec, G1V 4G2
    Canada

    Site Not Available

  • Starship Children's Hospital

    Grafton, Auckland 1145
    New Zealand

    Site Not Available

  • Christchurch Hospital

    Christchurch, 8011
    New Zealand

    Site Not Available

  • HIMA San Pablo Oncologic Hospital

    Caguas, 00726
    Puerto Rico

    Site Not Available

  • University Pediatric Hospital

    San Juan, 00926
    Puerto Rico

    Site Not Available

  • Children's Hospital of Alabama

    Birmingham, Alabama 35233
    United States

    Site Not Available

  • USA Health Strada Patient Care Center

    Mobile, Alabama 36604
    United States

    Site Not Available

  • Providence Alaska Medical Center

    Anchorage, Alaska 99508
    United States

    Site Not Available

  • Banner Children's at Desert

    Mesa, Arizona 85202
    United States

    Site Not Available

  • Phoenix Childrens Hospital

    Phoenix, Arizona 85016
    United States

    Site Not Available

  • Banner University Medical Center - Tucson

    Tucson, Arizona 85719
    United States

    Site Not Available

  • Arkansas Children's Hospital

    Little Rock, Arkansas 72202-3591
    United States

    Site Not Available

  • Kaiser Permanente Downey Medical Center

    Downey, California 90242
    United States

    Site Not Available

  • City of Hope Comprehensive Cancer Center

    Duarte, California 91010
    United States

    Site Not Available

  • Loma Linda University Medical Center

    Loma Linda, California 92354
    United States

    Site Not Available

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California 90806
    United States

    Site Not Available

  • Cedars Sinai Medical Center

    Los Angeles, California 90048
    United States

    Site Not Available

  • Children's Hospital Los Angeles

    Los Angeles, California 90027
    United States

    Site Not Available

  • Mattel Children's Hospital UCLA

    Los Angeles, California 90095
    United States

    Site Not Available

  • Valley Children's Hospital

    Madera, California 93636
    United States

    Site Not Available

  • Kaiser Permanente-Oakland

    Oakland, California 94611
    United States

    Site Not Available

  • UCSF Benioff Children's Hospital Oakland

    Oakland, California 94609
    United States

    Site Not Available

  • Children's Hospital of Orange County

    Orange, California 92868
    United States

    Site Not Available

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California 94304
    United States

    Site Not Available

  • Sutter Medical Center Sacramento

    Sacramento, California 95816
    United States

    Site Not Available

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California 95817
    United States

    Site Not Available

  • Naval Medical Center -San Diego

    San Diego, California 92134
    United States

    Site Not Available

  • Rady Children's Hospital - San Diego

    San Diego, California 92123
    United States

    Site Not Available

  • UCSF Medical Center-Mission Bay

    San Francisco, California 94158
    United States

    Site Not Available

  • Santa Barbara Cottage Hospital

    Santa Barbara, California 93102
    United States

    Site Not Available

  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

    Torrance, California 90502
    United States

    Site Not Available

  • Children's Hospital Colorado

    Aurora, Colorado 80045
    United States

    Site Not Available

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado 80218
    United States

    Site Not Available

  • Connecticut Children's Medical Center

    Hartford, Connecticut 06106
    United States

    Site Not Available

  • Yale University

    New Haven, Connecticut 06520
    United States

    Site Not Available

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware 19803
    United States

    Site Not Available

  • Children's National Medical Center

    Washington, District of Columbia 20010
    United States

    Site Not Available

  • MedStar Georgetown University Hospital

    Washington, District of Columbia 20007
    United States

    Site Not Available

  • Broward Health Medical Center

    Fort Lauderdale, Florida 33316
    United States

    Site Not Available

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida 33908
    United States

    Site Not Available

  • University of Florida Health Science Center - Gainesville

    Gainesville, Florida 32610
    United States

    Site Not Available

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida 33021
    United States

    Site Not Available

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida 32207
    United States

    Site Not Available

  • Palms West Radiation Therapy

    Loxahatchee Groves, Florida 33470
    United States

    Site Not Available

  • Miami Cancer Institute

    Miami, Florida 33176
    United States

    Site Not Available

  • Nicklaus Children's Hospital

    Miami, Florida 33155
    United States

    Site Not Available

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida 33136
    United States

    Site Not Available

  • AdventHealth Orlando

    Orlando, Florida 32803
    United States

    Site Not Available

  • Arnold Palmer Hospital for Children

    Orlando, Florida 32806
    United States

    Site Not Available

  • Nemours Children's Hospital

    Orlando, Florida 32827
    United States

    Site Not Available

  • Sacred Heart Hospital

    Pensacola, Florida 32504
    United States

    Site Not Available

  • Johns Hopkins All Children's Hospital

    Saint Petersburg, Florida 33701
    United States

    Site Not Available

  • Saint Joseph's Hospital/Children's Hospital-Tampa

    Tampa, Florida 33607
    United States

    Site Not Available

  • Tampa General Hospital

    Tampa, Florida 33606
    United States

    Site Not Available

  • Saint Mary's Hospital

    West Palm Beach, Florida 33407
    United States

    Site Not Available

  • Saint Mary's Medical Center

    West Palm Beach, Florida 33407
    United States

    Site Not Available

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia 30329
    United States

    Site Not Available

  • Children's Healthcare of Atlanta - Egleston

    Atlanta, Georgia 30322
    United States

    Site Not Available

  • Augusta University Medical Center

    Augusta, Georgia 30912
    United States

    Site Not Available

  • Atrium Health Navicent

    Macon, Georgia 31201
    United States

    Site Not Available

  • Medical Center of Central Georgia

    Macon, Georgia 31201
    United States

    Active - Recruiting

  • Memorial Health University Medical Center

    Savannah, Georgia 31404
    United States

    Site Not Available

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii 96826
    United States

    Site Not Available

  • Tripler Army Medical Center

    Honolulu, Hawaii 96859
    United States

    Site Not Available

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho 83712
    United States

    Site Not Available

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois 60611
    United States

    Site Not Available

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois 60637
    United States

    Site Not Available

  • University of Illinois

    Chicago, Illinois 60612
    United States

    Site Not Available

  • Loyola University Medical Center

    Maywood, Illinois 60153
    United States

    Site Not Available

  • Advocate Children's Hospital-Oak Lawn

    Oak Lawn, Illinois 60453
    United States

    Site Not Available

  • Advocate Children's Hospital-Park Ridge

    Park Ridge, Illinois 60068
    United States

    Site Not Available

  • Saint Jude Midwest Affiliate

    Peoria, Illinois 61637
    United States

    Site Not Available

  • Southern Illinois University School of Medicine

    Springfield, Illinois 62702
    United States

    Site Not Available

  • Northwestern Medicine Central DuPage Hospital

    Winfield, Illinois 60190
    United States

    Site Not Available

  • Ascension Saint Vincent Indianapolis Hospital

    Indianapolis, Indiana 46260
    United States

    Site Not Available

  • Riley Hospital for Children

    Indianapolis, Indiana 46202
    United States

    Site Not Available

  • Blank Children's Hospital

    Des Moines, Iowa 50309
    United States

    Site Not Available

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa 52242
    United States

    Site Not Available

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky 40536
    United States

    Site Not Available

  • Norton Children's Hospital

    Louisville, Kentucky 40202
    United States

    Site Not Available

  • Children's Hospital New Orleans

    New Orleans, Louisiana 70118
    United States

    Site Not Available

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana 70121
    United States

    Site Not Available

  • Eastern Maine Medical Center

    Bangor, Maine 04401
    United States

    Site Not Available

  • Maine Children's Cancer Program

    Scarborough, Maine 04074
    United States

    Site Not Available

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland 21287
    United States

    Site Not Available

  • Sinai Hospital of Baltimore

    Baltimore, Maryland 21215
    United States

    Site Not Available

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland 21201
    United States

    Site Not Available

  • Walter Reed National Military Medical Center

    Bethesda, Maryland 20889-5600
    United States

    Site Not Available

  • Dana-Farber Cancer Institute

    Boston, Massachusetts 02215
    United States

    Site Not Available

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts 02114
    United States

    Site Not Available

  • Tufts Children's Hospital

    Boston, Massachusetts 02111
    United States

    Site Not Available

  • Baystate Medical Center

    Springfield, Massachusetts 01199
    United States

    Site Not Available

  • UMass Memorial Medical Center - University Campus

    Worcester, Massachusetts 01655
    United States

    Site Not Available

  • C S Mott Children's Hospital

    Ann Arbor, Michigan 48109
    United States

    Site Not Available

  • Ascension Saint John Hospital

    Detroit, Michigan 48236
    United States

    Site Not Available

  • Children's Hospital of Michigan

    Detroit, Michigan 48201
    United States

    Site Not Available

  • Henry Ford Health Saint John Hospital

    Detroit, Michigan 48236
    United States

    Site Not Available

  • Michigan State University Clinical Center

    East Lansing, Michigan 48824
    United States

    Site Not Available

  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

    Grand Rapids, Michigan 49503
    United States

    Site Not Available

  • Helen DeVos Children's Hospital at Spectrum Health

    Grand Rapids, Michigan 49503
    United States

    Active - Recruiting

  • Bronson Methodist Hospital

    Kalamazoo, Michigan 49007
    United States

    Site Not Available

  • Beaumont Children's Hospital-Royal Oak

    Royal Oak, Michigan 48073
    United States

    Active - Recruiting

  • Corewell Health Children's

    Royal Oak, Michigan 48073
    United States

    Site Not Available

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota 55404
    United States

    Site Not Available

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota 55455
    United States

    Site Not Available

  • Mayo Clinic in Rochester

    Rochester, Minnesota 55905
    United States

    Site Not Available

  • University of Mississippi Medical Center

    Jackson, Mississippi 39216
    United States

    Site Not Available

  • Columbia Regional

    Columbia, Missouri 65201
    United States

    Active - Recruiting

  • University of Missouri Children's Hospital

    Columbia, Missouri 65212
    United States

    Site Not Available

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri 64108
    United States

    Site Not Available

  • Cardinal Glennon Children's Medical Center

    Saint Louis, Missouri 63104
    United States

    Site Not Available

  • Mercy Hospital Saint Louis

    Saint Louis, Missouri 63141
    United States

    Site Not Available

  • Washington University School of Medicine

    Saint Louis, Missouri 63110
    United States

    Site Not Available

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska 68114
    United States

    Site Not Available

  • University of Nebraska Medical Center

    Omaha, Nebraska 68198
    United States

    Site Not Available

  • Alliance for Childhood Diseases/Cure 4 the Kids Foundation

    Las Vegas, Nevada 89135
    United States

    Site Not Available

  • Summerlin Hospital Medical Center

    Las Vegas, Nevada 89144
    United States

    Site Not Available

  • Sunrise Hospital and Medical Center

    Las Vegas, Nevada 89109
    United States

    Site Not Available

  • University Medical Center of Southern Nevada

    Las Vegas, Nevada 89102
    United States

    Site Not Available

  • Renown Regional Medical Center

    Reno, Nevada 89502
    United States

    Site Not Available

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire 03756
    United States

    Site Not Available

  • Hackensack University Medical Center

    Hackensack, New Jersey 07601
    United States

    Site Not Available

  • Morristown Medical Center

    Morristown, New Jersey 07960
    United States

    Site Not Available

  • Jersey Shore Medical Center

    Neptune, New Jersey 07753
    United States

    Site Not Available

  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

    New Brunswick, New Jersey 08903
    United States

    Site Not Available

  • Saint Peter's University Hospital

    New Brunswick, New Jersey 08901
    United States

    Site Not Available

  • Newark Beth Israel Medical Center

    Newark, New Jersey 07112
    United States

    Site Not Available

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey 07503
    United States

    Site Not Available

  • Presbyterian Hospital

    Albuquerque, New Mexico 87106
    United States

    Site Not Available

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico 87106
    United States

    Site Not Available

  • Albany Medical Center

    Albany, New York 12208
    United States

    Site Not Available

  • Montefiore Medical Center - Moses Campus

    Bronx, New York 10467
    United States

    Site Not Available

  • Maimonides Medical Center

    Brooklyn, New York 11219
    United States

    Site Not Available

  • NYU Langone Hospital - Long Island

    Mineola, New York 11501
    United States

    Site Not Available

  • NYU Winthrop Hospital

    Mineola, New York 11501
    United States

    Active - Recruiting

  • The Steven and Alexandra Cohen Children's Medical Center of New York

    New Hyde Park, New York 11040
    United States

    Site Not Available

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York 10016
    United States

    Site Not Available

  • Memorial Sloan Kettering Cancer Center

    New York, New York 10065
    United States

    Site Not Available

  • Mount Sinai Hospital

    New York, New York 10029
    United States

    Site Not Available

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York 10032
    United States

    Site Not Available

  • NYP/Weill Cornell Medical Center

    New York, New York 10065
    United States

    Site Not Available

  • University of Rochester

    Rochester, New York 14642
    United States

    Site Not Available

  • Stony Brook University Medical Center

    Stony Brook, New York 11794
    United States

    Site Not Available

  • State University of New York Upstate Medical University

    Syracuse, New York 13210
    United States

    Site Not Available

  • New York Medical College

    Valhalla, New York 10595
    United States

    Site Not Available

  • Mission Hospital

    Asheville, North Carolina 28801
    United States

    Site Not Available

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina 27599
    United States

    Site Not Available

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina 28203
    United States

    Site Not Available

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina 28204
    United States

    Site Not Available

  • Duke University Medical Center

    Durham, North Carolina 27710
    United States

    Site Not Available

  • East Carolina University

    Greenville, North Carolina 27834
    United States

    Site Not Available

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina 27157
    United States

    Site Not Available

  • Sanford Broadway Medical Center

    Fargo, North Dakota 58122
    United States

    Site Not Available

  • Children's Hospital Medical Center of Akron

    Akron, Ohio 44308
    United States

    Site Not Available

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio 45229
    United States

    Site Not Available

  • Cleveland Clinic Foundation

    Cleveland, Ohio 44195
    United States

    Site Not Available

  • Rainbow Babies and Childrens Hospital

    Cleveland, Ohio 44106
    United States

    Site Not Available

  • Nationwide Children's Hospital

    Columbus, Ohio 43205
    United States

    Site Not Available

  • Dayton Children's Hospital

    Dayton, Ohio 45404
    United States

    Site Not Available

  • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

    Toledo, Ohio 43606
    United States

    Site Not Available

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma 73104
    United States

    Site Not Available

  • Natalie Warren Bryant Cancer Center at Saint Francis

    Tulsa, Oklahoma 74136
    United States

    Site Not Available

  • Legacy Emanuel Children's Hospital

    Portland, Oregon 97227
    United States

    Site Not Available

  • Oregon Health and Science University

    Portland, Oregon 97239
    United States

    Site Not Available

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania 18103
    United States

    Site Not Available

  • Geisinger Medical Center

    Danville, Pennsylvania 17822
    United States

    Site Not Available

  • Penn State Children's Hospital

    Hershey, Pennsylvania 17033
    United States

    Site Not Available

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania 19104
    United States

    Site Not Available

  • Saint Christopher's Hospital for Children

    Philadelphia, Pennsylvania 19134
    United States

    Site Not Available

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania 15224
    United States

    Site Not Available

  • Rhode Island Hospital

    Providence, Rhode Island 02903
    United States

    Site Not Available

  • Medical University of South Carolina

    Charleston, South Carolina 29425
    United States

    Site Not Available

  • Prisma Health Richland Hospital

    Columbia, South Carolina 29203
    United States

    Site Not Available

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina 29605
    United States

    Site Not Available

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota 57117-5134
    United States

    Site Not Available

  • T C Thompson Children's Hospital

    Chattanooga, Tennessee 37403
    United States

    Site Not Available

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee 37916
    United States

    Site Not Available

  • The Children's Hospital at TriStar Centennial

    Nashville, Tennessee 37203
    United States

    Site Not Available

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee 37232
    United States

    Site Not Available

  • Texas Tech University Health Sciences Center-Amarillo

    Amarillo, Texas 79106
    United States

    Site Not Available

  • Dell Children's Medical Center of Central Texas

    Austin, Texas 78723
    United States

    Site Not Available

  • Driscoll Children's Hospital

    Corpus Christi, Texas 78411
    United States

    Site Not Available

  • Medical City Dallas Hospital

    Dallas, Texas 75230
    United States

    Site Not Available

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas 75390
    United States

    Site Not Available

  • El Paso Children's Hospital

    El Paso, Texas 79905
    United States

    Site Not Available

  • Cook Children's Medical Center

    Fort Worth, Texas 76104
    United States

    Site Not Available

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas 77030
    United States

    Site Not Available

  • M D Anderson Cancer Center

    Houston, Texas 77030
    United States

    Site Not Available

  • Covenant Children's Hospital

    Lubbock, Texas 79410
    United States

    Site Not Available

  • UMC Cancer Center / UMC Health System

    Lubbock, Texas 79415
    United States

    Site Not Available

  • Vannie Cook Children's Clinic

    McAllen, Texas 78503
    United States

    Site Not Available

  • Children's Hospital of San Antonio

    San Antonio, Texas 78207
    United States

    Site Not Available

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas 78229
    United States

    Site Not Available

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas 78229
    United States

    Site Not Available

  • Scott and White Memorial Hospital

    Temple, Texas 76508
    United States

    Site Not Available

  • Primary Children's Hospital

    Salt Lake City, Utah 84113
    United States

    Site Not Available

  • University of Vermont and State Agricultural College

    Burlington, Vermont 05405
    United States

    Site Not Available

  • University of Virginia Cancer Center

    Charlottesville, Virginia 22908
    United States

    Site Not Available

  • Inova Fairfax Hospital

    Falls Church, Virginia 22042
    United States

    Site Not Available

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia 23507
    United States

    Site Not Available

  • Naval Medical Center - Portsmouth

    Portsmouth, Virginia 23708-2197
    United States

    Site Not Available

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia 23298
    United States

    Site Not Available

  • Carilion Children's

    Roanoke, Virginia 24014
    United States

    Site Not Available

  • Seattle Children's Hospital

    Seattle, Washington 98105
    United States

    Site Not Available

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington 99204
    United States

    Site Not Available

  • Madigan Army Medical Center

    Tacoma, Washington 98431
    United States

    Site Not Available

  • Mary Bridge Children's Hospital and Health Center

    Tacoma, Washington 98405
    United States

    Site Not Available

  • West Virginia University Charleston Division

    Charleston, West Virginia 25304
    United States

    Site Not Available

  • Edwards Comprehensive Cancer Center

    Huntington, West Virginia 25701
    United States

    Site Not Available

  • West Virginia University Healthcare

    Morgantown, West Virginia 26506
    United States

    Site Not Available

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin 54301
    United States

    Site Not Available

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin 53792
    United States

    Active - Recruiting

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin 53792
    United States

    Site Not Available

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin 54449
    United States

    Site Not Available

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin 53226
    United States

    Site Not Available

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