Leukemia
Conditions
Keywords
chronic myelomonocytic leukemia
Brief summary
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
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
Interventions
Sponsors
Study design
Eligibility
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability | — |
| Overall response rate | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival | — |
| Progression-free survival | — |
| Incidence of clinical remission/complete remission or partial response according to International Working Group (IWG) criteria | — |
| Time to death or AML transformation of CMML | — |
| Biological correlates | — |
| Time to acute myeloid leukemia (AML) transformation of CMML | — |
| Hematological improvement according to IWG criteria | — |
Countries
United Kingdom