Clinical trial NCT01235117: Azacitidine in Treating Patients With Chronic Myelomonocytic Leukemia
Official title: A Phase 2 Study of Azacitidine in Chronic Myelomonocytic Leukemia (CMML)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: chronic myelomonocytic leukemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2010-11-05
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: Safety and tolerability
measure: Overall response rate
Secondary outcomes:
measure: Incidence of clinical remission/complete remission or partial response according to International Working Group (IWG) criteria
measure: Hematological improvement according to IWG criteria
measure: Overall survival
measure: Progression-free survival
measure: Time to acute myeloid leukemia (AML) transformation of CMML
measure: Time to death or AML transformation of CMML
measure: Biological correlates
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
Study officials:
affiliation: Leeds Cancer Centre at St. James's University Hospital
name: David T. Bowen, MD
role: PRINCIPAL_INVESTIGATOR
References: