Blinatumomab, Inotuzumab Ozogamicin, and Combination Chemotherapy as Frontline Therapy in Treating Patients With B Acute Lymphoblastic Leukemia

Last updated: May 18, 2026
Sponsor: M.D. Anderson Cancer Center
Overall Status: Active - Recruiting

Phase

2

Condition

Leukemia

Marginal Zone Lymphoma

Lymphoma

Treatment

Methotrexate

Ofatumumab

Inotuzumab Ozogamicin

Clinical Study ID

NCT02877303
2014-0845
2014-0845
NCI-2017-00596
  • Ages > 14
  • All Genders

Study Summary

This phase II trial studies how well blinatumomab, inotuzumab ozogamicin, and combination chemotherapy work as frontline therapy in treating patients with B acute lymphoblastic leukemia. Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, cytarabine, mercaptopurine, methotrexate, and prednisone 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. Giving blinatumomab, inotuzumab ozogamicin, and combination chemotherapy may work better in treating patients with B acute lymphoblastic leukemia than chemotherapy alone.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Patients with newly diagnosed, previously untreated B-lineage ALL or lymphoblasticlymphoma, or having achieved complete remission (CR) with one course of inductionchemotherapy; patients who require steroids, cytarabine (ara-c) or hydrea to managedisease symptoms prior to finalization of diagnosis and treatment plan are allowedand eligible

  • Failure to one induction course of chemotherapy (these patients will be analyzedseparately); patients who require steroids, ara-c or hydrea to manage diseasesymptoms prior to finalization of diagnosis and treatment plan are allowed andeligible

  • Performance status of 0-3

  • Creatinine less than or equal to 2.0 mg/dL (unless considered tumor related)

  • Bilirubin less than or equal to 2.0 mg/dL (unless considered tumor related)

  • Adequate cardiac function as assessed by history and physical examination

  • No active or co-existing malignancy with life expectancy less than 12 months,sources for the determination of clinical significance by the treating physicianwill be included in the subject's medical record

Exclusion

Exclusion Criteria:

  • Pregnant or nursing women

  • Known to be human immunodeficiency virus (HIV)-positive

  • Philadelphia chromosome (Ph)-positive ALL

  • Active and uncontrolled disease/infection as judged by the treating physician,sources for the determination of clinical significance by the treating physicianwill be included in the subject's medical record

  • Unable or unwilling to sign the consent form

  • Subjects who have current active hepatic or biliary disease (with exception ofpatients with Gilbert's syndrome, asymptomatic gallstones, liver metastases orstable chronic liver disease per treating physician assessment), sources for thedetermination of clinical significance by the treating physician will be included inthe subject's medical record

  • History or presence of clinically relevant central nervous system (CNS) pathologysuch as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe braininjuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome,or psychosis; (Patients with CNS involvement of leukemia are NOT excluded)

  • Current autoimmune disease or history of autoimmune disease with potential CNSinvolvement; auto-immune disease with possible CNS consequences/manifestations suchas such as epilepsy, paresis, aphasia, stroke, dementia, Parkinson's disease,cerebellar disease, or psychosis

Study Design

Total Participants: 80
Treatment Group(s): 13
Primary Treatment: Methotrexate
Phase: 2
Study Start date:
November 01, 2016
Estimated Completion Date:
November 01, 2026

Study Description

PRIMARY OBJECTIVE:

I. To evaluate the clinical efficacy of the sequential combination of hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) + blinatumomab + inotuzumab ozogamicin (inotuzumab) in patients with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) in terms of relapse-free survival (RFS).

SECONDARY OBJECTIVE:

I. To evaluate other efficacy endpoints such as overall survival, overall response rate, minimal residual disease (MRD) negativity rate as well as the safety of this combination.

EXPLORATORY OBJECTIVES:

I. To identify genomic alterations in adult ALL predictive for response and long-term outcomes with the combination of hyper-CVAD plus blinatumomab and inotuzumab.

II. To evaluate the impact of next generation sequencing (NGS)-based MRD assay on outcomes and to compare with standard flow cytometry MRD assays.

OUTLINE:

INTENSIVE PHASE: Patients receive cyclophosphamide intravenously (IV) over 3 hours twice daily (BID) on days 1-3, dexamethasone orally (PO) once daily (QD) on days 1-4 and 11-14, methotrexate intrathecally (IT) on day 2 of cycles 1 and 3, day 8 of cycles 2 and 4, and IV over 24 hours on day 1 of cycles 2 and 4, doxorubicin hydrochloride IV continuously on day 4, vincristine sulfate IV over 15 minutes on days 4 and 11, and cytarabine IT on day 7 of cycles 1 and 3, day 5 of cycles 2 and 4, and IV over 2 hours on days 2 and 3 of cycles 2 and 4. Patients may also receive ofatumumab IV or rituximab IV over 4-6 hours on days 1 and 11 of cycles 1 and 3, and days 1 and 8 of cycles 2 and 4 at the discretion of the treating physician. Patients may receive ofatumumab IV over 4-6 hours on day 2 of cycle 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

BLINATUMOMAB AND INOTUZUMAB OZOGAMICIN PHASE (CYCLES 5-8): Patients receive blinatumomab IV continuously on weeks 1-4. Patients also receive inotuzumab ozogamicin IV over 1 hour on days 5 and 11 of cycles 6 and 8. Treatment repeats every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: At doctor's discretion, patients may receive maintenance therapy prior to completing 4 cycles of hyper-CVAD and/or 4 cycles of blinatumomab. Patients receive mercaptopurine PO thrice daily (TID), methotrexate PO every week, vincristine sulfate IV over 15 minutes every month, and prednisone PO on days 1-5. Cycles repeat every 6 weeks for 12 months in the absence of disease progression or unacceptable toxicity. Patients also receive blinatumomab IV after every 3 cycles of maintenance therapy for a total of about 15 cycles.

After completion of study treatment, patients are followed up 1 time each month for up to 24 months.

Connect with a study center

  • M D Anderson Cancer Center

    Houston, Texas 77030
    United States

    Active - Recruiting

  • M D Anderson Cancer Center

    Houston 4699066, Texas 4736286 77030
    United States

    Site Not Available

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