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Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Older Patients with Previously Untreated Acute Lymphoblastic Leukemia

Trial Status: Active

This phase I / II trial studies the side effects and best dose of inotuzumab ozogamicin and to see how well it works when given together with combination chemotherapy in treating older patients with previously untreated acute lymphoblastic leukemia. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called N-acetyl-gamma-calicheamicin dimethyl hydrazide (CalichDMH). Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers CalichDMH to kill them. Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy 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 inotuzumab ozogamicin together with combination chemotherapy may be a better treatment for acute lymphoblastic leukemia.

Inclusion Criteria

  • Patients with previously untreated ALL pre-B, Philadelphia chromosome (Ph-) negative or (Ph+) positive ALL; minimal prior therapy (less than 1 week of steroids, vincristine, and/or 1 dose of anthracycline or alkylating agents) are allowed
  • Zubrod performance status 0-3
  • Bilirubin =< 1.95 mg/dL
  • Serum glutamate pyruvate transaminase (SGPT) or serum glutamic oxaloacetic transaminase (SGOT) =< 3 x upper limit of normal (ULN) unless considered due to tumor
  • Creatinine =< 2 mg/dL
  • Even if organ function abnormalities are considered due to tumor, the upper limit for bilirubin is =< 2.6 mg/dL and creatinine =< 3 mg/dL
  • Provision of written informed consent
  • Patients in first remission are eligible
  • Patients with refractory-relapsed ALL of any age are eligible

Exclusion Criteria

  • Burkitt’s leukemia or lymphoma, T-cell ALL or lymphoblastic lymphoma
  • Patient with active heart disease (New York Heart Association [NYHA] class >= 3 as assessed by history and physical examination)
  • Patients with a cardiac ejection fraction (as measured by either multigated acquisition scan [MUGA] or echocardiogram) < 40% are excluded
  • Patients with active hepatitis are excluded
  • Pregnant or breast-feeding women are excluded

Texas

Houston
M D Anderson Cancer Center
Status: ACTIVE
Contact: Elias Jabbour
Phone: 713-792-7026

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in combination with low-intensity chemotherapy in elderly patients (age 60 or older) with acute lymphoblastic leukemia (ALL). (Phase I)

II. Evaluate the efficacy of inotuzumab ozogamicin in combination with low-intensity chemotherapy in elderly patients with ALL. (Phase II)

III. To evaluate the side effects of the treatment. (Phase II)

IV. Evaluate the regimen efficacy in refractory-relapsed ALL. (Phase II)

EXPLORATORY OBJECTIVES:

I. To identify genomic alterations in adult ALL predictive for response and long-term outcomes with the combination of hyper-CVD (cyclophosphamide, dexamethasone, methotrexate, and cytarabine) + inotuzumab + blinatumomab.

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

OUTLINE: This is a phase I, dose-escalation study of inotuzumab ozogamicin followed by a phase II study.

CYCLES 1, 3, 7, AND 9: Patients receive cyclophosphamide intravenously (IV) over approximately 3 hours twice daily (BID) on days 1-3; vincristine sulfate IV over 30 minutes on days 1 and 8; inotuzumab ozogamicin IV over approximately 1 hour on day 3 of cycle 1 and day 2 or 3 of cycle 3; methotrexate intrathecally (IT) on day 2 of cycles 1 and 3; and cytarabine IT on day 8 of cycles 1 and 3. Patients may also receive rituximab IV on days 1 and 8 of cycles 1 and 3. Cycles alternate every 3-4 weeks in the absence of disease progression or unacceptable toxicity.

CYCLES 2, 4, 8, AND 10: Patients receive methotrexate IV over approximately 2 hours and then continuously over approximately 22 hours on day 1; cytarabine IV over approximately 3 hours BID on days 2-3; inotuzumab ozogamicin IV over approximately 1 hour on day 2 or 3 of cycles 2 and 4; cytarabine IT on day 5 of cycles 2 and 4; and methotrexate IT on day 8 of cycles 2 and 4. Patients may also receive rituximab IV on days 1 and 8 of cycles 2 and 4. Cycles alternate every 3-4 weeks in the absence of disease progression or unacceptable toxicity.

CYCLES 5, 6, 11, AND 12: Patients receive blinatumomab as a continuous intravenous infusion (CIVI) on days 1-29. Treatment repeats every 42 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive mercaptopurine orally (PO) BID and methotrexate PO once weekly for 3 years. Patients also receive vincristine sulfate IV over 30 minutes once monthly and prednisone PO daily five times a month for 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who did not receive blinatumomab during induction and consolidation can receive 4 consecutive cycles of blinatumomab as in cycles 5, 6, 11, and 12, at any time during maintenance, after discussion with the principal investigator and if in the best interest of the patient.

TREATMENT OF MINIMAL RESIDUAL DISEASE (MRD): Patients with MRD may receive additional cycles of inotuzumab ozogamicin IV every 3-4 weeks for up to 6 doses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 4 months.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
M D Anderson Cancer Center

Principal Investigator
Elias Jabbour

  • Primary ID 2010-0991
  • Secondary IDs NCI-2011-01123
  • Clinicaltrials.gov ID NCT01371630