Gemtuzumab Ozogamicin and Cyclosporine in Treating Older Patients With Relapsed 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. Cyclosporine may increase the effectiveness of gemtuzumab ozogamicin by making cancer cells more sensitive to the drug. Combining gemtuzumab ozogamicin with cyclosporine may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving gemtuzumab ozogamicin together with cyclosporine works in treating older patients with relapsed acute myeloid leukemia.

Detailed Description
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OBJECTIVES: Primary Determine the efficacy of gemtuzumab ozogamicin and cyclosporine, in terms of the complete remission rate, in older patients with relapsed acute myeloid leukemia. Determine the toxicity and pharmacokinetics of this regimen in these patients. Secondary Correlate clinical response with laboratory studies of drug susceptibility in patients treated with this regimen. OUTLINE: Patients receive cyclosporine IV continuously over 72 hours on days 1-3 and 15-17. Eight hours after initiation of each cyclosporine infusion, patients receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed for survival. PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study within 3 years.

Official Title
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A Phase II Trial Combining Gemtuzumab Ozogamicin (Mylotarg) With Cyclosporine for the Treatment of Relapsed Acute Myeloid Leukemia in Adults Over Age 60

Conditions
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Leukemia

Intervention / Treatment
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* Drug: cyclosporine
* Drug: gemtuzumab ozogamicin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Morphologically confirmed acute myeloid leukemia (AML) by bone marrow aspirate More than 20% blasts by morphologic criteria Relapsed disease ≥ 3 months after prior complete remission Blasts CD33-positive by flow cytometry No primary hematologic disorder that preceded initial presentation with AML No documented secondary AML related to prior chemotherapy or toxin exposure No acute promyelocytic leukemia (FAB M3) Not a candidate for transplant therapy No active CNS leukemia PATIENT CHARACTERISTICS: Age 60 and over Performance status Karnofsky 70-100% Life expectancy Not specified Hematopoietic WBC ≤ 30,000/mm^3 (hydroxyurea allowed) Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST or ALT ≤ 1.5 times ULN Renal Creatinine ≤ 1.5 mg/dL Other HIV negative No uncontrolled infection PRIOR CONCURRENT THERAPY: Biologic therapy Not planning hematopoietic stem cell transplantation immediately after study therapy Chemotherapy See Disease Characteristics See Hematopoietic Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other More than 1 month since prior investigational agents No other concurrent anticancer therapy No administration of any of the following for 24 hours after cyclosporine administration: Diltiazem Verapamil Erythromycin Clarithromycin Metoclopramide Phenytoin Rifampin Phenobarbital Aminoglycosides Amphotericin B Vancomycin Cimetidine Ranitidine Trimethoprim/sulfamethoxazole Ketoconazole Fluconazole Itraconazole Voriconazole Carbamazepine

Ages Eligible for Study
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Minimum Age: 60 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cyclosporine|nan|
|Drug: gemtuzumab ozogamicin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy in terms of complete remission rate |  |  | 
| Toxicity |  |  | 
| Pharmacokinetics |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlate clinical response to laboratory studies of drug susceptibility |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult acute myeloid leukemia, adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloblastic leukemia with maturation (M2), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute megakaryoblastic leukemia (M7), adult acute basophilic leukemia, adult acute eosinophilic leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22)