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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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A Dose Escalation And Phase II Study Of Gemtuzumab Ozogamicin (CMA-676; Mylotarg) With High-Dose Cytarabine For Patients With Refractory Or Relapsed Acute Myeloid Leukemia (AML)

Conditions
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Leukemia

Intervention / Treatment
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* Drug: ara-C
* Biological: gemtuzumab ozogamicin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort I<br>Immunotherapy with gemtuzumab | Biological: gemtuzumab ozogamicin<br>* 9 mg/sq m IV infusion over 2 hrs D 1 (Cohort I); D 7 (Cohorts II, IA, & IV); & D 14 (Cohort IV) 4.5 mg/sq m IV infusion over 2 hrs D 8 (Cohort I) & D 14 (Cohort II)<br>* Other names: Mylotarg;|
| Experimental: Cohort II<br>Gemtuzumab + ara-C | Drug: ara-C<br>* 3 g/sq m IV infusion over 3 hours Days 1-5<br>* Other names: Cytarabine;Biological: gemtuzumab ozogamicin<br>* 9 mg/sq m IV infusion over 2 hrs D 1 (Cohort I); D 7 (Cohorts II, IA, & IV); & D 14 (Cohort IV) 4.5 mg/sq m IV infusion over 2 hrs D 8 (Cohort I) & D 14 (Cohort II)<br>* Other names: Mylotarg;|
| Experimental: Cohort IA<br>Gemtuzumab + ara C | Drug: ara-C<br>* 3 g/sq m IV infusion over 3 hours Days 1-5<br>* Other names: Cytarabine;Biological: gemtuzumab ozogamicin<br>* 9 mg/sq m IV infusion over 2 hrs D 1 (Cohort I); D 7 (Cohorts II, IA, & IV); & D 14 (Cohort IV) 4.5 mg/sq m IV infusion over 2 hrs D 8 (Cohort I) & D 14 (Cohort II)<br>* Other names: Mylotarg;|
| Experimental: Cohort IV<br>Gemtuzumab + ara-C | Drug: ara-C<br>* 3 g/sq m IV infusion over 3 hours Days 1-5<br>* Other names: Cytarabine;Biological: gemtuzumab ozogamicin<br>* 9 mg/sq m IV infusion over 2 hrs D 1 (Cohort I); D 7 (Cohorts II, IA, & IV); & D 14 (Cohort IV) 4.5 mg/sq m IV infusion over 2 hrs D 8 (Cohort I) & D 14 (Cohort II)<br>* Other names: Mylotarg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate |  | 8 or 14 days after tx initiation & 30 d post tx | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | D 14, then 30, 60 , & 90 d post Tx, q 3 mon for 1 yr, then at relapse or death | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult acute myeloid leukemia