Azacitidine in Treating Patients With Chronic Myelomonocytic Leukemia

University of Leeds

Status and phase: Completed; Phase 2

Conditions: Leukemia

Treatments: Other: laboratory biomarker analysis; Drug: azacitidine

Study type: Interventional

Funder types: Other

Identifiers

NCT01235117

LEEDS-HM08/8540

ISRCTN-21428905

EU-21082

EUDRACT-2008-006349-23

CTRU-CMML-201

CDR0000688119

Details and patient eligibility

About

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.

Full 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

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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