Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia

Last updated: August 23, 2016
Sponsor: Children's Oncology Group
Overall Status: Active - Recruiting

Phase

3

Condition

Pain

Leukemia

Musculoskeletal Diseases

Treatment

Doxorubicin Hydrochloride

Leucovorin Calcium

Methotrexate

Clinical Study ID

NCT01406756
AALL1131
AALL1131
CDR0000706370
U10CA180886
NCI-2011-03797
COG-AALL1131
U10CA098543
  • Ages 1-30
  • Both

Study Summary

This randomized phase III trial is studying how well combination chemotherapy works in treating young patients with newly diagnosed acute lymphoblastic leukemia that is likely to come back or spread. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Patients must be enrolled on AALL08B1 prior to enrollment on AALL1131

  • White Blood Cell Count (WBC) Criteria

  • Age 1-9.99 years: WBC >= 50 000/uL

  • Age 10-30.99 years: Any WBC

  • Age 1-30.99 years: Any WBC with:

  • Testicular leukemia

  • CNS leukemia (CNS3)

  • Steroid pretreatment

  • Patients must have newly diagnosed B lymphoblastic leukemia (2008 World HealthOrganization [WHO] classification) (also termed B-precursor acute lymphoblasticleukemia); patients with Down syndrome are also eligible

  • Eligibility criteria for the Incidence and Natural History of Osteonecrosis study

  • Patients must be 10 years of age or greater at the time of B-ALL diagnosis,enrolled on AALL1131

  • Patients with Down syndrome are not eligible

  • Eligibility criteria for the Longitudinal, Computerized Assessment of NeurocognitiveFunctioning study

  • Patients must be aged 6 to 11 years at time of B-ALL diagnosis, enrolled onAALL1131

  • Patients must be English-, French- or Spanish-speaking (languages in which theassessment is available)

  • Patients must have no known history of neurodevelopmental disorder prior todiagnosis of B-ALL (e.g., Down syndrome, Fragile X, William's Syndrome, mentalretardation)

  • Patients must have no significant visual impairment that would prevent computeruse and recognition of the visual test stimuli

  • Eligibility criteria for the National Cancer Institute (NCI) standard risk patientsfrom AALL0932 enrolling on this study at the end of Induction:

  • Patients enrolled on AALL0932, without Down syndrome, meeting the following criteriawill NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the HRB-ALL stratum of this study at the end of Induction:

  • Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), withday 8 peripheral blood (PB) minimal residual disease (MRD) >= 1% and day 29 BMMRD < 0.01%

  • With favorable cytogenetics (ETV6-RUNX1 or double trisomies 4+10), with any day 8 PB MRD and day 29 bone marrow (BM) MRD >= 0.01%

  • Both NCI standard risk (SR) and HR patients without Down syndrome and withtesticular disease at diagnosis, who do not meet other VHR criteria, will beeligible for the HR stratum

  • Patients enrolled on AALL0932, without Down syndrome, meeting the following criteriawill NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on theVHR B-ALL stratum of this study at the end of Induction:

  • Intrachromosomal amplification of chromosome 21 (iAMP21)

  • Mixed-lineage leukemia (MLL) rearrangement

  • Hypodiploidy (n < 44 chromosomes and/or a deoxyribonucleic acid [DNA] index < 0.81)

  • Induction failure (M3 BM at day 29)

  • Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), withday 29 BM MRD >= 0.01%

  • Patients enrolled on AALL0932, with Down syndrome, meeting the following criteriawill NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the DSHR B-ALL stratum of this study at the end of Induction:

  • Day 29 MRD >= 0.01%

  • MLL rearrangement

  • Hypodiploidy (n < 45 chromosomes and/or DNA index < 0.81)

  • DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Inductionfailure (M3 BM day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible forpost-Induction therapy on either trial (AALL0932 or AALL1131)

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

  • All institutional, Food and Drug Administration (FDA), and NCI requirements for humanstudies must be met

Exclusion

Exclusion Criteria:

  • 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 any cancer diagnosed prior to the initiationof protocol therapy on AALL1131; patients cannot have secondary B-ALL that developedafter treatment of a prior malignancy with cytotoxic chemotherapy; patients receivingprior steroid therapy may be eligible for AALL1131

  • Patients with breakpoint cluster region (BCR)-v-abl Abelson murine leukemia viraloncogene homolog 1 (ABL1) fusion (not eligible for post-Induction therapy on thisstudy; non-DS patients may be eligible to enroll in AALL1122 or successor Children'sOncology Group [COG] Philadelphia positive [Ph+] ALL trial by day 15 Induction)

  • DS HR B-ALL patients with Induction failure or BCR-ABL1

  • Female patients who are pregnant are ineligible

  • Lactating females are not eligible unless they have agreed not to breastfeed theirinfant

  • Female patients of childbearing potential are not eligible unless a negativepregnancy test result has been obtained

  • Sexually active patients of reproductive potential are not eligible unless they haveagreed to use an effective contraceptive method for the duration of their studyparticipation

Study Design

Total Participants: 4895
Treatment Group(s): 16
Primary Treatment: Doxorubicin Hydrochloride
Phase: 3
Study Start date:
February 01, 2012
Estimated Completion Date:

Study Description

PRIMARY OBJECTIVES:

I. To determine if the administration of post-Induction age-adjusted intrathecal triple therapy (ITT) on a Modified Berlin-Frankfurt-Munster (MBFM) interim maintenance (IM) high-dose methotrexate (IMHDM) backbone will improve 5-year disease-free survival (DFS) of children with high-risk (HR) B-acute lymphoblastic leukemia (ALL) compared to age-adjusted intrathecal (IT) methotrexate (MTX).

II. To determine, in a randomized fashion, if the cyclophosphamide + etoposide containing regimen (Experimental Arm 1) will improve the 4-year DFS of children, adolescents, and young adults with very high-risk (VHR) B-ALL compared to a modified MBFM-IMHDM regimen that contains a second IM (Control Arm).

SECONDARY OBJECTIVES:

I. To determine the toxicity and tolerability of post-Induction age-adjusted ITT compared to age-adjusted IT MTX in children with HR B-ALL.

II. To determine the toxicity and tolerability of Experimental Arm 1 compared to the Control Arm in children, adolescents, and young adults with VHR B-ALL.

III. To determine whether a single-arm, modified Induction with limited anthracycline exposure and post-Induction therapy regimen with MBFM-IMIDM and reduced vincristine (vincristine sulfate)/steroid pulse frequency and enhanced supportive care in children with Down syndrome (DS) and HR B-ALL will result in a >= 65% 5-year DFS and < 10% Induction mortality.

IV. To determine the toxicity and tolerability of MBFM-IMIDM in children with DS and HR B-ALL.

V. To estimate overall survival (OS) rates both overall and by regimen a) for HR B-ALL and b) VHR B-ALL patients.

VI. To determine the incidence of osteonecrosis (ON), defined by magnetic resonance (MR) imaging, and to characterize the natural history of clinically silent ON in children, adolescents, and young adults 10 years of age and greater and to assess the role of drugs (i.e., asparaginase and methotrexate) in addition to corticosteroids, in the risk for development of ON.

VII. To determine if the prevalence of cognitive deficits measured by CogState, in children (ages 6 to 11 years) with HR- and VHR B-ALL at 1 year off therapy, is significantly higher than the normative population (> 14%) in the following domains: working memory, executive function, visual motor, processing speed, and visual attention.

TERTIARY OBJECTIVES:

I. To determine if the reduction of minimal residual disease (MRD) from end-Induction to end-Consolidation is greater for children, adolescents, and young adults with VHR B-ALL receiving Experimental Arm 1 compared to the Control Arm.

OUTLINE:

INDUCTION THERAPY:

Patients without Down syndrome receive induction chemotherapy comprising cytarabine intrathecally (IT) on day 1; vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, and 22; daunorubicin hydrochloride IV over 1-15 minutes on days 1, 8, 15, and 22; dexamethasone orally (PO) or IV twice daily (BID) on days 1-14 (patients under 10 years old) or prednisone PO or IV BID on days 1-28 (patients at least 10 years old); pegaspargase IV over 1-2 hours on day 4; and methotrexate IT on days 8 and 29 (plus days 15 and 22 for CNS3 patients). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY: Patients are randomized to 1 of 2 treatment arms.

ARM I HR B-ALL CONSOLIDATION (C): Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO once daily (QD) on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; and pegaspargase IV over 1-2 hours on days 15 and 43. Patients with continuing clinical evidence of testicular leukemia undergo radiotherapy (RT) QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

ARM II HR B-ALL C: Patients receive Consolidation therapy as in Arm I HR B-ALL C. Patients also receive ITT comprising methotrexate, hydrocortisone sodium succinate, and cytarabine on days 1, 8, 15, and 22. Patients with testicular leukemia also undergo RT as in Arm I HR B-ALL C.

INTERIM MAINTENANCE THERAPY:

ARM I HR B-ALL INTERIM MAINTENANCE (IM): Patients receive IM therapy comprising vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; methotrexate IT on days 1 and 29; and mercaptopurine PO on days 1-56. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

ARM II HR B-ALL IM: Patients receive ITT on days 1 and 29 and IM therapy as in Arm I HR-ALL IM. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION THERAPY:

ARM I HR B-ALL DELAYED INTENSIFICATION (DI): Patients receive DI therapy comprising vincristine sulfate IV over 1 hour on days 1, 8, 15, 43, and 50; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-60 minutes on days 1, 8, and 15; methotrexate IT on days 1, 29, and 36; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO QD on days 29-42. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

ARM II HR B-ALL DI: Patients receive ITT on days 1, 29, and 36 and DI therapy as in Arm I HR B-ALL DI.

MAINTENANCE (M) THERAPY:

ARM I HR B-ALL M: Patients receive maintenance therapy comprising vincristine sulfate IV over 1 minute on days 1, 29, and 57; methotrexate IT on day 1 (also day 29 of courses 1-4); prednisone PO BID on days 1-5, 29-33 (may receive methylprednisolone IV if PO is not tolerated), and 57-61; mercaptopurine PO QD on days 1-84; and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity.

ARM II HR B-ALL M: Patients receive ITT on day 1 (also day 29 of courses 1-4) and maintenance therapy as in Arm I HR B-ALL M. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity.

VERY HIGH-RISK B-ALL: Patients are randomized to 1 of 3 treatment arms.

CONSOLIDATION THERAPY PART I: In all arms, patients receive cyclophosphamide IV over 30-60 minutes on day 1; cytarabine IV or SC on days 1-4 and 8-11; mercaptopurine PO QD on days 1-14; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 patients); vincristine sulfate IV over 1 minute on days 15 and 22; and pegaspargase IV over 1-2 hours on day 15. Patients with continuing clinical evidence of testicular leukemia undergo RT QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY PART II:

ARM A VHR B-ALL C (CONTROL ARM): Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; mercaptopurine PO QD on days 29-42; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

ARM B VHR B-ALL C (EXPERIMENTAL ARM): Patients receive consolidation therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on days 29-33; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

ARM C VHR B-ALL C: Patients receive clofarabine IV over 2 hours on days 29-33 and consolidation therapy as in Arm B VHR B-ALL C. (Closed as of 9/12/2014)

INTERIM MAINTENANCE I: In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION PART I: In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 8, and 15; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-60 minutes on days 1, 8, and 15; methotrexate IT on day 1; and pegaspargase IV over 1-2 hours on day 4. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION PART II:

ARM A VHR B-ALL DI (CONTROL ARM): Patients receive DI therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; thioguanine PO QD on days 29-42; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

ARM B VHR B-ALL DI (EXPERIMENTAL ARM): Patients receive DI therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on days 29-33; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

ARM C VHR B-ALL DI: Patients receive clofarabine IV over 2 hours on days 29-33 and DI therapy as in Arm II B VHR B-ALL DI. (Closed as of 9/12/2014)

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

MAINENTANCE THERAPY: Patients with CNS3 disease at diagnosis undergo RT QD over 4 weeks (10 fractions total). In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61 (may receive methylprednisolone IV if PO is not tolerated); methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (except on methotrexate IT days); mercaptopurine PO QD on days 1-84; methotrexate IT on day 1 (also day 29 of courses 1 and 2 for CNS patients who did not undergo RT). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicities.

INDUCTION THERAPY: All patients receive cytarabine IT on day 1; vincristine sulfate IV over 1 minute on days 1 and 8, dexamethasone PO or IV BID (patients under 10 years old) or prednisone PO BID (patients at least 10 years old) on days 1-14 (may receive methylprednisolone IV if PO is not tolerated), pegaspargase IV over 1-2 hours on day 4; methotrexate IT on day 8; and leucovorin calcium PO on days 10-11. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

Rapid early responders (RER): Patients receive induction therapy comprising vincristine sulfate IV over 1 minute on days 15 and 22; dexamethasone PO BID or prednisone PO BID on days 15-28; methotrexate IT on day 29 (also days 15 and 22 for CNS3 patients); and leucovorin calcium PO on days 31-32 (also days 17-18 and 24-25 for CNS3 patients). Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

Slow early responders (SER): Patients receive daunorubicin hydrochloride IV over 1-15 minutes on day 15 and Induction therapy as RER patients. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY: All 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; mercaptopurine PO QD on days 1-14 and 29-42; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; pegaspargase IV over 1-2 hours on days 15 and 43; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 patients); and leucovorin calcium PO on days 3-4, 10-11, 17-18, and 24-25. Patients with continuing clinical evidence of testicular leukemia undergo RT QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

INTERIM MAINTENANCE THERAPY: Patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; intermediate dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION THERAPY: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 43, and 50; dexamethasone PO BID or IV on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-60 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO QD on days 29-42; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; methotrexate IT on days 1, 29, and 36; and leucovorin calcium PO on days 3-4, 31-32 and 38-39.

MAINTENANCE THERAPY: Patients with CNS3 disease undergo RT QD, 5 days a week, for 2 weeks (10 fractions total). Patients receive vincristine sulfate IV over 1 minute on day 1; prednisone PO BID or IV on days 1-5 (may receive methylprednisolone IV if PO not tolerated); methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO QD on days 1-84; and methotrexate IT on day 1 (also day 29 of courses 1-4 for CNS3 patients who did not undergo RT). Treatment repeats every 12 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 10 years.

Connect with a study center

  • John Hunter Children's Hospital

    Hunter Regional Mail Centre, New South Wales 2310
    Australia

    Active - Recruiting

  • Royal Children's Hospital

    Brisbane, Queensland 4029
    Australia

    Site Not Available

  • Royal Brisbane and Women's Hospital

    Herston, Queensland 4029
    Australia

    Active - Recruiting

  • Royal Children's Hospital-Brisbane

    Herston, Queensland 4029
    Australia

    Site Not Available

  • Lady Cilento Children's Hospital

    South Brisbane, Queensland 4101
    Australia

    Active - Recruiting

  • Monash Medical Center-Clayton Campus

    Clayton, Victoria 3168
    Australia

    Active - Recruiting

  • Royal Children's Hospital

    Parkville, Victoria 3052
    Australia

    Active - Recruiting

  • Princess Margaret Hospital for Children

    Perth, Western Australia 6008
    Australia

    Active - Recruiting

  • Alberta Children's Hospital

    Calgary, Alberta T3B 6A8
    Canada

    Active - Recruiting

  • University of Alberta Hospital

    Edmonton, Alberta T6G 2B7
    Canada

    Active - Recruiting

  • British Columbia Children's Hospital

    Vancouver, British Columbia V6H 3V4
    Canada

    Active - Recruiting

  • CancerCare Manitoba

    Winnipeg, Manitoba R3E 0V9
    Canada

    Active - Recruiting

  • Janeway Child Health Centre

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

    Active - Recruiting

  • Janeway Children's Health and Rehabilitation Centre

    St. John's, Newfoundland and Labrador A1B 3V6
    Canada

    Site Not Available

  • IWK Health Centre

    Halifax, Nova Scotia B3K 6R8
    Canada

    Active - Recruiting

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario L8N 3Z5
    Canada

    Active - Recruiting

  • Cancer Centre of Southeastern Ontario at Kingston General Hospital

    Kingston, Ontario K7L 5P9
    Canada

    Active - Recruiting

  • Children's Hospital

    London, Ontario N6A 5W9
    Canada

    Active - Recruiting

  • Children's Hospital of Eastern Ontario

    Ottawa, Ontario K1H 8L1
    Canada

    Active - Recruiting

  • Hospital for Sick Children

    Toronto, Ontario M5G 1X8
    Canada

    Active - Recruiting

  • The Montreal Children's Hospital of the MUHC

    Montreal, Quebec H3H 1P3
    Canada

    Site Not Available

  • Allan Blair Cancer Centre

    Regina, Saskatchewan S4T 7T1
    Canada

    Site Not Available

  • Saskatoon Cancer Centre

    Saskatoon, Saskatchewan S7N 4H4
    Canada

    Active - Recruiting

  • Our Lady's Children's Hospital

    Dublin, Co Dublin 12
    Ireland

    Active - Recruiting

  • Starship Children's Hospital

    Grafton, Auckland 1145
    New Zealand

    Active - Recruiting

  • Starship Children's Health

    Auckland, 1
    New Zealand

    Site Not Available

  • Christchurch Hospital

    Christchurch, 8011
    New Zealand

    Active - Recruiting

  • San Jorge Children's Hospital

    San Juan, 00912
    Puerto Rico

    Active - Recruiting

  • University Pediatric Hospital

    San Juan, 00926
    Puerto Rico

    Active - Recruiting

  • Swiss Pediatric Oncology Group - Geneva

    Geneva, 1205
    Switzerland

    Active - Recruiting

  • Swiss Pediatric Oncology Group - Lausanne

    Lausanne, 1011
    Switzerland

    Active - Recruiting

  • Children's Hospital of Alabama

    Birmingham, Alabama 35233
    United States

    Active - Recruiting

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama 35233
    United States

    Site Not Available

  • University of South Alabama

    Mobile, Alabama 36604
    United States

    Active - Recruiting

  • Providence Alaska Medical Center

    Anchorage, Alaska 99508
    United States

    Active - Recruiting

  • Cardon Children's Medical Center

    Mesa, Arizona 85202
    United States

    Active - Recruiting

  • Phoenix Childrens Hospital

    Phoenix, Arizona 85016
    United States

    Active - Recruiting

  • The University of Arizona Medical Center-University Campus

    Tucson, Arizona 85724
    United States

    Active - Recruiting

  • Arkansas Children's Hospital

    Little Rock, Arkansas 72202-3591
    United States

    Active - Recruiting

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas 72205
    United States

    Site Not Available

  • Children's Oncology Group

    Arcadia, California 91006-3776
    United States

    Site Not Available

  • Southern California Permanente Medical Group

    Downey, California 90242
    United States

    Active - Recruiting

  • City of Hope Comprehensive Cancer Center

    Duarte, California 91010
    United States

    Active - Recruiting

  • Loma Linda University Medical Center

    Loma Linda, California 92354
    United States

    Active - Recruiting

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

    Long Beach, California 90806
    United States

    Active - Recruiting

  • Cedars-Sinai Medical Center

    Los Angeles, California 90048
    United States

    Active - Recruiting

  • Children's Hospital Los Angeles

    Los Angeles, California 90027
    United States

    Active - Recruiting

  • Mattel Children's Hospital UCLA

    Los Angeles, California 90095
    United States

    Active - Recruiting

  • Children's Hospital Central California

    Madera, California 93636-8762
    United States

    Active - Recruiting

  • Children's Hospital and Research Center at Oakland

    Oakland, California 94609-1809
    United States

    Active - Recruiting

  • Kaiser Permanente-Oakland

    Oakland, California 94611
    United States

    Active - Recruiting

  • Children's Hospital of Orange County

    Orange, California 92868
    United States

    Active - Recruiting

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California 94304
    United States

    Active - Recruiting

  • Sutter General Hospital

    Sacramento, California 95816
    United States

    Active - Recruiting

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California 95817
    United States

    Active - Recruiting

  • Naval Medical Center -San Diego

    San Diego, California 92134
    United States

    Active - Recruiting

  • Rady Children's Hospital - San Diego

    San Diego, California 92123
    United States

    Active - Recruiting

  • UCSF Medical Center-Mission Bay

    San Francisco, California 94158
    United States

    Active - Recruiting

  • UCSF Medical Center-Parnassus

    San Francisco, California 94143
    United States

    Site Not Available

  • Santa Barbara Cottage Hospital

    Santa Barbara, California 93102
    United States

    Active - Recruiting

  • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

    Torrance, California 90502
    United States

    Active - Recruiting

  • Children's Hospital Colorado

    Aurora, Colorado 80045
    United States

    Active - Recruiting

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

    Denver, Colorado 80218
    United States

    Active - Recruiting

  • Connecticut Children's Medical Center

    Hartford, Connecticut 06106
    United States

    Active - Recruiting

  • Yale University

    New Haven, Connecticut 06520
    United States

    Active - Recruiting

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware 19803
    United States

    Active - Recruiting

  • Children's National Medical Center

    Washington, District of Columbia 20010
    United States

    Active - Recruiting

  • MedStar Georgetown University Hospital

    Washington, District of Columbia 20007
    United States

    Active - Recruiting

  • Broward Health Medical Center

    Fort Lauderdale, Florida 33316
    United States

    Active - Recruiting

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida 33908
    United States

    Active - Recruiting

  • Lee Memorial Health System

    Fort Myers, Florida 33901
    United States

    Site Not Available

  • University of Florida

    Gainesville, Florida 32610
    United States

    Active - Recruiting

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida 33021
    United States

    Active - Recruiting

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida 32207
    United States

    Active - Recruiting

  • Baptist Hospital of Miami

    Miami, Florida 33176
    United States

    Active - Recruiting

  • Nicklaus Children's Hospital

    Miami, Florida 33155
    United States

    Active - Recruiting

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

    Miami, Florida 33136
    United States

    Terminated

  • Arnold Palmer Hospital for Children

    Orlando, Florida 32806
    United States

    Active - Recruiting

  • Florida Hospital Orlando

    Orlando, Florida 32803
    United States

    Active - Recruiting

  • Nemours Children's Clinic - Orlando

    Orlando, Florida 32806
    United States

    Site Not Available

  • Nemours Children's Hospital

    Orlando, Florida 32827
    United States

    Active - Recruiting

  • UF Cancer Center at Orlando Health

    Orlando, Florida 32806
    United States

    Site Not Available

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida 32504
    United States

    Active - Recruiting

  • All Children's Hospital

    Saint Petersburg, Florida 33701
    United States

    Active - Recruiting

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

    Tampa, Florida 33607
    United States

    Active - Recruiting

  • Tampa General Hospital

    Tampa, Florida 33606
    United States

    Active - Recruiting

  • Saint Mary's Hospital

    West Palm Beach, Florida 33407
    United States

    Active - Recruiting

  • Children's Healthcare of Atlanta - Egleston

    Atlanta, Georgia 30322
    United States

    Active - Recruiting

  • Georgia Regents University Medical Center

    Augusta, Georgia 30912
    United States

    Active - Recruiting

  • Memorial University Medical Center

    Savannah, Georgia 31404
    United States

    Active - Recruiting

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii 96826
    United States

    Active - Recruiting

  • Tripler Army Medical Center

    Honolulu, Hawaii 96859
    United States

    Terminated

  • University of Hawaii Cancer Center

    Honolulu, Hawaii 96813
    United States

    Site Not Available

  • Saint Luke's Mountain States Tumor Institute

    Boise, Idaho 83712
    United States

    Active - Recruiting

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois 60611
    United States

    Active - Recruiting

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois 60637
    United States

    Active - Recruiting

  • University of Illinois

    Chicago, Illinois 60612
    United States

    Active - Recruiting

  • Loyola University Medical Center

    Maywood, Illinois 60153
    United States

    Active - Recruiting

  • Advocate Children's Hospital-Oak Lawn

    Oak Lawn, Illinois 60453
    United States

    Active - Recruiting

  • Advocate Children's Hospital-Park Ridge

    Park Ridge, Illinois 60068
    United States

    Active - Recruiting

  • Advocate Lutheran General Hospital

    Park Ridge, Illinois 60068
    United States

    Site Not Available

  • Saint Jude Midwest Affiliate

    Peoria, Illinois 61637
    United States

    Active - Recruiting

  • Southern Illinois University School of Medicine

    Springfield, Illinois 62702
    United States

    Active - Recruiting

  • Riley Hospital for Children

    Indianapolis, Indiana 46202
    United States

    Active - Recruiting

  • Saint Vincent Hospital and Health Care Center

    Indianapolis, Indiana 46260
    United States

    Active - Recruiting

  • Blank Children's Hospital

    Des Moines, Iowa 50309
    United States

    Active - Recruiting

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa 52242
    United States

    Active - Recruiting

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky 40536
    United States

    Active - Recruiting

  • Kosair Children's Hospital

    Louisville, Kentucky 40202
    United States

    Active - Recruiting

  • Tulane Cancer Center Office of Clinical Research

    Alexandria, Louisiana 71315-3198
    United States

    Site Not Available

  • Children's Hospital New Orleans

    New Orleans, Louisiana 70118
    United States

    Active - Recruiting

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana 70121
    United States

    Active - Recruiting

  • Tulane University Health Sciences Center

    New Orleans, Louisiana 70112
    United States

    Site Not Available

  • Eastern Maine Medical Center

    Bangor, Maine 04401
    United States

    Active - Recruiting

  • Maine Children's Cancer Program

    Scarborough, Maine 04074
    United States

    Active - Recruiting

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland 21287
    United States

    Active - Recruiting

  • Sinai Hospital of Baltimore

    Baltimore, Maryland 21215
    United States

    Active - Recruiting

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland 21201
    United States

    Active - Recruiting

  • Walter Reed National Military Medical Center

    Bethesda, Maryland 20889-5600
    United States

    Active - Recruiting

  • Floating Hospital for Children at Tufts Medical Center

    Boston, Massachusetts 02111
    United States

    Active - Recruiting

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts 02114
    United States

    Active - Recruiting

  • Baystate Medical Center

    Springfield, Massachusetts 01199
    United States

    Active - Recruiting

  • University of Massachusetts Medical School

    Worcester, Massachusetts 01655
    United States

    Active - Recruiting

  • C S Mott Children's Hospital

    Ann Arbor, Michigan 48109
    United States

    Active - Recruiting

  • Saint John Hospital and Medical Center

    Detroit, Michigan 48236
    United States

    Active - Recruiting

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan 48201
    United States

    Active - Recruiting

  • Michigan State University Clinical Center

    East Lansing, Michigan 48824-7016
    United States

    Active - Recruiting

  • Hurley Medical Center

    Flint, Michigan 48502
    United States

    Active - Recruiting

  • Helen DeVos Children's Hospital at Spectrum Health

    Grand Rapids, Michigan 49503
    United States

    Active - Recruiting

  • Van Elslander Cancer Center at St. John Hospital and Medical Center

    Grosse Pointe Woods, Michigan 48236
    United States

    Site Not Available

  • Bronson Methodist Hospital

    Kalamazoo, Michigan 49007
    United States

    Active - Recruiting

  • Michigan State University - Breslin Cancer Center

    Lansing, Michigan 48910
    United States

    Site Not Available

  • Beaumont Children's Hospital-Royal Oak

    Royal Oak, Michigan 48073
    United States

    Active - Recruiting

  • William Beaumont Hospital-Royal Oak

    Royal Oak, Michigan 48073
    United States

    Site Not Available

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota 55404
    United States

    Active - Recruiting

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota 55455
    United States

    Active - Recruiting

  • Mayo Clinic

    Rochester, Minnesota 55905
    United States

    Active - Recruiting

  • University of Mississippi Medical Center

    Jackson, Mississippi 39216
    United States

    Active - Recruiting

  • Columbia Regional

    Columbia, Missouri 65201
    United States

    Active - Recruiting

  • University of Missouri - Ellis Fischel

    Columbia, Missouri 65212
    United States

    Site Not Available

  • The Childrens Mercy Hospital

    Kansas City, Missouri 64108
    United States

    Active - Recruiting

  • Cardinal Glennon Children's Medical Center

    Saint Louis, Missouri 63104
    United States

    Active - Recruiting

  • Mercy Hospital Saint Louis

    Saint Louis, Missouri 63141
    United States

    Active - Recruiting

  • Washington University School of Medicine

    Saint Louis, Missouri 63110
    United States

    Active - Recruiting

  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    St. Louis, Missouri 63110
    United States

    Site Not Available

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska 68114
    United States

    Active - Recruiting

  • University of Nebraska Medical Center

    Omaha, Nebraska 68198
    United States

    Active - Recruiting

  • Children's Specialty Center of Nevada II

    Las Vegas, Nevada 89109
    United States

    Active - Recruiting

  • Nevada Cancer Research Foundation CCOP

    Las Vegas, Nevada 89106
    United States

    Active - Recruiting

  • Summerlin Hospital Medical Center

    Las Vegas, Nevada 89144
    United States

    Active - Recruiting

  • Sunrise Hospital and Medical Center

    Las Vegas, Nevada 89109
    United States

    Active - Recruiting

  • University Medical Center of Southern Nevada

    Las Vegas, Nevada 89102
    United States

    Active - Recruiting

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire 03756
    United States

    Active - Recruiting

  • Hackensack University Medical Center

    Hackensack, New Jersey 07601
    United States

    Active - Recruiting

  • Saint Barnabas Medical Center

    Livingston, New Jersey 07039
    United States

    Site Not Available

  • Morristown Medical Center

    Morristown, New Jersey 07960
    United States

    Active - Recruiting

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

    New Brunswick, New Jersey 08903
    United States

    Active - Recruiting

  • Saint Peter's University Hospital

    New Brunswick, New Jersey 08901
    United States

    Active - Recruiting

  • Newark Beth Israel Medical Center

    Newark, New Jersey 07112
    United States

    Active - Recruiting

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey 07503
    United States

    Active - Recruiting

  • Overlook Hospital

    Summit, New Jersey 07902
    United States

    Active - Recruiting

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico 87106
    United States

    Active - Recruiting

  • Albany Medical Center

    Albany, New York 12208
    United States

    Active - Recruiting

  • Montefiore Medical Center - Moses Campus

    Bronx, New York 10467-2490
    United States

    Active - Recruiting

  • Roswell Park Cancer Institute

    Buffalo, New York 14263
    United States

    Active - Recruiting

  • Winthrop University 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

    Active - Recruiting

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York 10016
    United States

    Active - Recruiting

  • Mount Sinai Medical Center

    New York, New York 10029
    United States

    Active - Recruiting

  • Weill Medical College of Cornell University

    New York, New York 10065
    United States

    Active - Recruiting

  • University of Rochester

    Rochester, New York 14642
    United States

    Active - Recruiting

  • Stony Brook University Medical Center

    Stony Brook, New York 11794
    United States

    Active - Recruiting

  • State University of New York Upstate Medical University

    Syracuse, New York 13210
    United States

    Active - Recruiting

  • New York Medical College

    Valhalla, New York 10595
    United States

    Active - Recruiting

  • Mission Hospital-Memorial Campus

    Asheville, North Carolina 28801
    United States

    Active - Recruiting

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina 27599
    United States

    Active - Recruiting

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina 28203
    United States

    Active - Recruiting

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina 28204
    United States

    Active - Recruiting

  • Duke University Medical Center

    Durham, North Carolina 27710
    United States

    Active - Recruiting

  • East Carolina University

    Greenville, North Carolina 27858
    United States

    Active - Recruiting

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina 27157
    United States

    Active - Recruiting

  • Sanford Medical Center-Fargo

    Fargo, North Dakota 58122
    United States

    Active - Recruiting

  • Children's Hospital Medical Center of Akron

    Akron, Ohio 44308
    United States

    Active - Recruiting

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio 45229
    United States

    Active - Recruiting

  • Cleveland Clinic Foundation

    Cleveland, Ohio 44195
    United States

    Active - Recruiting

  • Rainbow Babies and Childrens Hospital

    Cleveland, Ohio 44106
    United States

    Active - Recruiting

  • Nationwide Children's Hospital

    Columbus, Ohio 43205
    United States

    Active - Recruiting

  • Dayton Children's Hospital

    Dayton, Ohio 45404
    United States

    Active - Recruiting

  • Mercy Children's Hospital

    Toledo, Ohio 43608
    United States

    Terminated

  • The Toledo Hospital/Toledo Children's Hospital

    Toledo, Ohio 43606
    United States

    Active - Recruiting

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma 73104
    United States

    Active - Recruiting

  • Natalie Warren Bryant Cancer Center at Saint Francis

    Tulsa, Oklahoma 74136
    United States

    Active - Recruiting

  • Legacy Emanuel Children's Hospital

    Portland, Oregon 97227
    United States

    Active - Recruiting

  • Oregon Health and Science University

    Portland, Oregon 97239
    United States

    Active - Recruiting

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania 18017
    United States

    Active - Recruiting

  • Geisinger Medical Center

    Danville, Pennsylvania 17822
    United States

    Active - Recruiting

  • Penn State Hershey Children's Hospital

    Hershey, Pennsylvania 17033
    United States

    Active - Recruiting

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania 19104
    United States

    Active - Recruiting

  • Saint Christopher's Hospital for Children

    Philadelphia, Pennsylvania 19134
    United States

    Active - Recruiting

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania 15224
    United States

    Active - Recruiting

  • Rhode Island Hospital

    Providence, Rhode Island 02903
    United States

    Active - Recruiting

  • Medical University of South Carolina

    Charleston, South Carolina 29425
    United States

    Active - Recruiting

  • Palmetto Health Richland

    Columbia, South Carolina 29203
    United States

    Active - Recruiting

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina 29605
    United States

    Active - Recruiting

  • Greenville Cancer Treatment Center

    Greenville, South Carolina 29605
    United States

    Active - Recruiting

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota 57117-5134
    United States

    Active - Recruiting

  • T C Thompson Children's Hospital

    Chattanooga, Tennessee 37403
    United States

    Active - Recruiting

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee 37916
    United States

    Active - Recruiting

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee 37232
    United States

    Active - Recruiting

  • Texas Tech University Health Science Center-Amarillo

    Amarillo, Texas 79106
    United States

    Site Not Available

  • Dell Children's Medical Center of Central Texas

    Austin, Texas 78723
    United States

    Active - Recruiting

  • Driscoll Children's Hospital

    Corpus Christi, Texas 78411
    United States

    Active - Recruiting

  • Medical City Dallas Hospital

    Dallas, Texas 75230
    United States

    Active - Recruiting

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas 75390
    United States

    Active - Recruiting

  • El Paso Children's Hospital

    El Paso, Texas 79905
    United States

    Active - Recruiting

  • Cook Children's Medical Center

    Fort Worth, Texas 76104
    United States

    Active - Recruiting

  • Baylor College of Medicine

    Houston, Texas 77030
    United States

    Active - Recruiting

  • M D Anderson Cancer Center

    Houston, Texas 77030
    United States

    Active - Recruiting

  • Covenant Children's Hospital

    Lubbock, Texas 79410
    United States

    Active - Recruiting

  • Vannie Cook Children's Clinic

    McAllen, Texas 78503
    United States

    Active - Recruiting

  • Children's Hospital of San Antonio

    San Antonio, Texas 78207
    United States

    Active - Recruiting

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas 78229
    United States

    Active - Recruiting

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas 78229
    United States

    Active - Recruiting

  • Scott and White Memorial Hospital

    Temple, Texas 76508
    United States

    Active - Recruiting

  • Primary Children's Hospital

    Salt Lake City, Utah 84113
    United States

    Active - Recruiting

  • University of Vermont College of Medicine

    Burlington, Vermont 05405
    United States

    Active - Recruiting

  • University of Virginia Cancer Center

    Charlottesville, Virginia 22908
    United States

    Active - Recruiting

  • Inova Fairfax Hospital

    Falls Church, Virginia 22042
    United States

    Active - Recruiting

  • Childrens Hospital-King's Daughters

    Norfolk, Virginia 23507
    United States

    Active - Recruiting

  • Naval Medical Center - Portsmouth

    Portsmouth, Virginia 23708-2197
    United States

    Active - Recruiting

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia 23298
    United States

    Active - Recruiting

  • Carilion Clinic Children's Hospital

    Roanoke, Virginia 24014
    United States

    Active - Recruiting

  • Seattle Children's Hospital

    Seattle, Washington 98105
    United States

    Active - Recruiting

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington 99204
    United States

    Active - Recruiting

  • Madigan Army Medical Center

    Tacoma, Washington 98431
    United States

    Active - Recruiting

  • Mary Bridge Children's Hospital and Health Center

    Tacoma, Washington 98405
    United States

    Active - Recruiting

  • West Virginia University Charleston

    Charleston, West Virginia 25304
    United States

    Active - Recruiting

  • West Virginia University Healthcare

    Morgantown, West Virginia 26506
    United States

    Active - Recruiting

  • Saint Vincent Hospital

    Green Bay, Wisconsin 54301
    United States

    Active - Recruiting

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin 53792
    United States

    Active - Recruiting

  • Marshfield Clinic

    Marshfield, Wisconsin 54449
    United States

    Active - Recruiting

  • Midwest Children's Cancer Center

    Milwaukee, Wisconsin 53226
    United States

    Active - Recruiting

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