Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated 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. It is not yet known whether gemtuzumab ozogamicin is more effective than standard supportive care in treating older patients who have acute myeloid leukemia. PURPOSE: This randomized phase II/III trial is studying two different gemtuzumab ozogamicin regimens to see how well they work compared to standard supportive care in treating older patients with previously untreated acute myeloid leukemia.

Detailed Description
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OBJECTIVES: Compare the feasibility, toxicity, and antileukemic activity of two different dosing regimens of gemtuzumab ozogamicin (GO) vs standard supportive care in older patients with previously untreated acute myeloid leukemia who are not candidates for intensive chemotherapy. (phase II) Compare the efficacy and toxicity of the best dosing regimen of GO selected from phase II vs standard supportive care, in terms of overall survival, in these patients. (phase III) OUTLINE: This is a randomized, open-label, multicenter phase II study followed by a phase III study. Patients are stratified according to age (61 to 75 vs 76 to 80 vs 81 and over), CD33-positivity of bone marrow blasts (< 20% vs 20-80% vs > 80% vs unknown), initial WBC before hydroxyurea administration (< 30,000/mm^3 vs ≥ 30,000/mm^3), WHO performance status (0-1 vs 2 vs 3-4), and participating center. Phase II: Patients are randomized to 1 of 3 treatment arms. Arm I: Patients receive gemtuzumab ozogamicin (GO) IV over 2 hours on days 1 and 8. Patients with stable or responding disease at day 36 receive GO IV over 2 hours every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive GO IV over 2 hours on days 1, 3, and 5. Patients with stable or responding disease at day 36 receive GO IV over 2 hours every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Arm III: Patients receive standard supportive care. Phase III: Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive the selected treatment (arm I or arm II) from phase II. Arm II: Patients receive standard supportive care. Patients who receive GO treatment are followed monthly for 1 year and then every 3 months thereafter. Patients who receive standard supportive care are followed at least every 4 weeks. PROJECTED ACCRUAL: A total of 259 patients (75 for phase II [25 per treatment arm] and 184 for phase III [92 per treatment arm]) will be accrued for this study within 2.5 years.

Official Title
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Gemtuzumab Ozogamicin (GO) Monotherapy Versus Standard Supportive Care for Previously Untreated AML in Elderly Patients Who Are Not Eligible for Intensive Chemotherapy: A Randomized Phase II/III Trial (AML-19) of the EORTC-LG and GIMEMA-ALWP

Conditions
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Leukemia

Intervention / Treatment
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* Drug: gemtuzumab ozogamicin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed acute myeloid leukemia (AML) At least 20% bone marrow blasts by bone marrow aspiration or biopsy All subtypes except M3 (acute promyelocytic leukemia) are allowed Previously untreated primary or secondary disease (including AML after myelodysplastic syndromes) Ineligible for intensive chemotherapy, as defined by 1 of the following criteria: 61 to 75 years old AND WHO performance status > 2 AND/OR unwilling to receive intensive chemotherapy Over 75 years old No blast crisis of chronic myeloid leukemia No AML supervention after other myeloproliferative disease WBC < 30,000/mm^3 and meets 1 of the following criteria: WBC < 30,000/mm^3 at diagnosis AND had no prior treatment with hydroxyurea WBC ≥ 30,000/mm^3 at diagnosis AND received mandatory pretreatment with hydroxyurea (up to 14 days duration) until WBC < 30,000/mm^3 No active CNS leukemia PATIENT CHARACTERISTICS: Age See Disease Characteristics 61 and over Performance status See Disease Characteristics Life expectancy Not specified Hematopoietic See Disease Characteristics Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) Renal Creatinine ≤ 1.5 times ULN Cardiovascular No arrhythmia requiring chronic treatment No congestive heart failure No symptomatic ischemic heart disease No other severe cardiovascular disease Pulmonary No severe pulmonary dysfunction ≥ grade 3 Other No alcohol abuse No severe neurological or psychiatric disease No active uncontrolled infection or severe systemic infection No other malignancy No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) No concurrent antiangiogenic drugs Chemotherapy See Disease Characteristics Concurrent low-dose cytostatic agents (i.e., thioguanine or mercaptopurine) allowed for palliative care (standard supportive care arm only) Endocrine therapy Prior corticosteroids (duration ≤ 14 days ) for primary or secondary AML allowed Radiotherapy Not specified Surgery Not specified Other No other concurrent cytotoxic drugs No other concurrent experimental therapy No concurrent tyrosine kinase inhibitors

Ages Eligible for Study
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Minimum Age: 61 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients able to start continuation therapy (Phase II) |  |  | 
| Overall survival (Phase III) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete remission (CR+CRp)by the end of continuation therapy, for patients in the GO arms (Phase II) |  |  | 
| Overall survival (Phase II) |  |  | 
| Toxicity (CTCAE grading), including time to hematological recovery (Phase II & III) |  |  | 
| Rate of complete remisison (CR+CRp) by the end of induction and by the end of continuation therapy, for patients in GO arm (Phase III) |  |  | 
| Disease-free survival for patients who reached CR or CRp (Phase III) |  |  | 
| Progression-free survival from randomization for patients in GO arm (Phase III) |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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), untreated adult acute myeloid leukemia, secondary acute myeloid leukemia, adult acute basophilic leukemia, adult acute eosinophilic leukemia, adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute megakaryoblastic leukemia (M7), adult acute minimally differentiated myeloid leukemia (M0), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myelomonocytic leukemia (M4)