Cilengitide in Treating Patients With Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This randomized phase II trial is studying how well cilengitide works in treating patients with acute myeloid leukemia. Cilengitide may stop the growth of cancer cells by blocking the enzymes necessary for their growth

Detailed Description
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PRIMARY OBJECTIVES: I. Determine 10-month relapse-free survival of patients with acute myeloid leukemia in first complete remission treated with cilengitide as maintenance therapy. SECONDARY OBJECTIVES: I. Determine overall survival of patients treated with this drug. II. Determine the safety and toxicity of this drug in these patients. III. Determine the biological activity of this drug in cells from these patients. OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive cilengitide IV at a lower dose over 1 hour twice weekly for 4 weeks. Arm II: Patients receive cilengitide IV at a higher dose over 1 hour twice weekly for 4 weeks. In both arms, courses repeat every 4 weeks in the absence of disease relapse or unacceptable toxicity.

Official Title
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A Phase 2 Study of EMD 121974 as Maintenance Therapy for Patinets With Acute Myeloid Leukemia in Complete Remission

Conditions
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Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, 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 Without Maturation (M1), Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b)

Intervention / Treatment
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* Drug: cilengitide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of acute myeloid leukemia (AML) In first complete remission after at least 1 course of induction chemotherapy AND 1-2 courses of consolidation chemotherapy for newly diagnosed AML, as defined by the following: No evidence of disease in bone marrow Recovery of peripheral blood counts Platelet count > 100,000/mm^3 Absolute neutrophil count > 1,500/mm^3 Must be able to start study medication within 60 days from the start of the last consolidation therapy Must not have a suitable donor, refused, or ineligible for hematopoietic stem call transplantation None of the following AML subtypes or chromosomal translocations: Acute promyelocytic leukemia t(8;21) t(16;16) inv(16) Performance status - ECOG 0-2 Performance status - Karnofsky 60-100% See Disease Characteristics Bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT ≤ 2.5 times ULN Creatinine ≤ 1.5 times ULN Creatinine clearance > 60mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness No prior investigational agents specifically designated as an antiangiogenic agent No concurrent prophylactic hematopoietic colony-stimulating factors See Disease Characteristics Recovered from prior consolidation chemotherapy No other concurrent anticancer therapies No other concurrent investigational cytotoxic agents

Ages Eligible for Study
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Minimum Age: 50 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (low dose cilengitide)<br>Patients receive cilengitide IV at a lower dose over 1 hour twice weekly for 4 weeks. | Drug: cilengitide<br>* Given IV<br>* Other names: EMD 121974;|
| Experimental: Arm II (higher dose cilengitide)<br>Patients receive cilengitide IV at a higher dose over 1 hour twice weekly for 4 weeks. | Drug: cilengitide<br>* Given IV<br>* Other names: EMD 121974;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS) | Kaplan-Meier curves will be constructed for each treatment group. Median DFS in each group and corresponding 95% confidence intervals will be estimated. The two treatment groups will be compared using log-rank test. | From initiation of induction chemotherapy until the first incidence of disease or death due to any cause, assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Analyzed using Kaplan-Meier life table methods and Cox proportional hazard regression modeling. | Up to 2 years | 
| Toxicity of cilengitide graded using the CTC version 3 | Compared between the two treatment arms using Fisher's exact test | Up to 2 years |