Gemtuzumab Ozogamicin and High-Dose Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Leukemia

Treatments: Drug: ara-C; Biological: gemtuzumab ozogamicin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00006265

CALGB-19902

U10CA031946 (U.S. NIH Grant/Contract)

CDR0000068208 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Monoclonal antibodies, such as gemtuzumab ozogamicin, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Combining gemtuzumab ozogamicin with cytarabine may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining gemtuzumab ozogamicin with high-dose cytarabine in treating patients who have relapsed or refractory acute myeloid leukemia.

Full description

OBJECTIVES:

• Determine the response rate in patients with relapsed or refractory acute myeloid leukemia treated with gemtuzumab ozogamicin (CMA-676) and high-dose cytarabine.
• Determine the safety and toxicity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of gemtuzumab ozogamicin (CMA-676) (phase I closed to accrual effective 08/25/2003). Patients are stratified according to disease status (refractory vs relapsed).

• Phase I (closed to accrual effective 08/25/2003): Patients are enrolled in one of four cohorts.

  • Cohort I (closed to accrual as of 10/1/02): Patients receive CMA-676 at the first dose level IV over 2 hours on days 1 and 8.
  • Cohort IA (open to accrual as of 10/15/02): Patients receive high-dose cytarabine (HD-ARA-C) IV over 3 hours on days 1-5 and CMA-676 IV over 2 hours on day 7.
  • Cohort II: Patients receive HD-ARA-C as in cohort IA and CMA-676 at the first dose level IV over 2 hours on days 7 and 14.
  • Cohort IV: Patients receive CMA-676 at the second dose level and HD-ARA-C as in cohort II.

Dose escalation stops if at least 3 of 9 patients experience dose-limiting toxicity.

• Phase II: Patients receive HD-ARA-C IV over 3 hours on days 1-5 and CMA-676 IV over 2 hours on day 7 (one course).

Patients are followed at 1 month, monthly for 6 months, every 3 months for 2 years, and then annually for 10 years.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for phase I of the study and a total of 37 patients will be accrued for phase II of the study within 2 years. (Phase I closed to accrual effective 08/25/2003).

Enrollment: 60 patients

Sex: All

Ages: 17+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• One of the following diagnoses:

  • Primary refractory acute myeloid leukemia (AML)

    • More than 10% blasts in the bone marrow or blood after recovery from 2 courses of standard cytarabine- and anthracycline-based induction chemotherapy
    • No prior remission

  • Relapsed AML

    • More than 10% blasts in the bone marrow or blood after documented remission
    • Prior remission lasted more than 30 days
    • No prior treatment for current relapse

• CD33 expression on at least 20% of leukemia blast cells at initial diagnosis for primary refractory patients or at the time of relapse for all other patients

• No active CNS involvement

PATIENT CHARACTERISTICS:

Age:

• 17 and over

Performance status:

• 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics
• WBC less than 30,000/mm^3

Hepatic:

• Bilirubin less than 2.0 mg/dL
• No veno-occlusive disease of the liver
• No chronic liver disease unless due to AML

Renal:

• Not specified

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active serious infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 6 months since prior stem cell transplantation

Chemotherapy:

• See Disease Characteristics
• Prior etoposide and/or thioguanine during remission induction allowed
• Prior hydroxyurea for control of AML allowed
• At least 24 hours since prior hydroxyurea
• At least 3 months since prior high-dose cytarabine (greater than 2 g/m^2/dose)-containing regimen
• No other concurrent chemotherapy

Endocrine therapy:

• Concurrent steroids for adrenal failure, hypersensitivity reactions, or septic shock allowed
• Concurrent ophthalmic corticosteroids allowed
• Concurrent hormones for nondisease-related conditions (e.g., insulin for diabetes or estrogens or progestins for gynecologic conditions) allowed

Radiotherapy:

• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• More than 2 months since prior cytotoxic therapy

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 4 patient groups

Cohort I

Experimental group

Description:

Immunotherapy with gemtuzumab

Treatment:

Biological: gemtuzumab ozogamicin

Cohort II

Experimental group

Description:

Gemtuzumab + ara-C

Treatment:

Biological: gemtuzumab ozogamicin

Drug: ara-C

Cohort IA

Experimental group

Description:

Gemtuzumab + ara C

Treatment:

Biological: gemtuzumab ozogamicin

Drug: ara-C

Cohort IV

Experimental group

Description:

Gemtuzumab + ara-C

Treatment:

Biological: gemtuzumab ozogamicin

Drug: ara-C