Azacitidine in Treating Patients With Chronic Myelomonocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying the side effects of azacitidine and to see how well it works in treating patients with chronic myelomonocytic leukemia.

Detailed Description
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OBJECTIVES: Primary To assess the safety and tolerability of azacitidine in patients with chronic myelomonocytic leukemia (CMML). To assess the overall response rate in these patients. Secondary To assess the incidence of clinical remission/complete remission or partial response in these patients. To assess hematological improvement in patients treated with this drug. To assess the overall survival of patients treated with this drug. To assess progression-free survival of patients treated with this drug. To assess the time to acute myeloid leukemia (AML) transformation of CMML. To assess the time to death or AML transformation of CMML. To assess the biological correlates. OUTLINE: This is a multicenter study. Patients receive azacitidine subcutaneously on days 1-5 and 8-9. Treatment repeats every 4 weeks for at least 6 courses in the absence of loss of response/disease progression or unacceptable toxicity. Patients undergo response evaluation after 6 courses or the last course of treatment. Responders may continue azacitidine until loss of response/disease progression or unacceptable toxicity. Some patients undergo blood, bone marrow, and buccal swab sample collection periodically for correlative studies. After completion of study treatment, patients are followed up for 1 month. Peer Reviewed and Funded or Endorsed by Cancer Research UK

Official Title
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A Phase 2 Study of Azacitidine in Chronic Myelomonocytic Leukemia (CMML)

Conditions
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Leukemia

Intervention / Treatment
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* Drug: azacitidine
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of 1 of the following: All chronic myelomonocytic leukemia (CMML)-2 patients CMML-1 patients meeting any of the following criteria: Symptomatic bone marrow failure/myeloproliferation defined as any of the following: Red cell transfusion dependence and pre-transfusion hemoglobin < 9.0 g/dL Symptomatic anemia (hemoglobin < 11.5 g/dL) Thrombocytopenia (platelet count < 50 x 10^9/L) Symptomatic bleeding due to platelet functional defect or disseminated intravascular coagulation (DIC)/fibrinolysis White cell count (WCC) > 50 x 10^9/L Düsseldorf Score of intermediate or high risk for proliferative CMML-1 (i.e., WCC > 12 x 10^9/L) International Prognostic Scoring System (IPSS) score of intermediate-2 or high risk for non-proliferative CMML-1 (i.e., WCC < 12 x 10^9/L) Systemic symptoms including weight loss with no alternative explanation (10% of baseline weight within the past 6 months) Symptomatic splenomegaly Symptomatic extramedullary involvement (e.g. skin infiltration or serous effusions) No CMML with eosinophilia and 5q33 abnormality PATIENT CHARACTERISTICS: WHO performance status 0-2 Creatinine ≤ 2 times upper limit of normal Not pregnant or nursing Negative urine pregnancy test Fertile patients must use at least 2 forms of effective contraception during study and for 3 months after completion of study therapy No other active malignant disease including basal cell or squamous cell carcinoma of the skin No known HIV or infectious hepatitis B or hepatitis C No active infection No known hypersensitivity to azacitidine or mannitol PRIOR CONCURRENT THERAPY: At least 28 days since other prior experimental drug or therapy No prior chemotherapy for this disease except hydroxycarbamide No other concurrent anticancer or investigational agents

Ages Eligible for Study
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Minimum Age: 18 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: azacitidine|nan|
|Other: laboratory biomarker analysis|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability |  |  | 
| Overall response rate |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of clinical remission/complete remission or partial response according to International Working Group (IWG) criteria |  |  | 
| Hematological improvement according to IWG criteria |  |  | 
| Overall survival |  |  | 
| Progression-free survival |  |  | 
| Time to acute myeloid leukemia (AML) transformation of CMML |  |  | 
| Time to death or AML transformation of CMML |  |  | 
| Biological correlates |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic myelomonocytic leukemia