Azacitidine in Treating Patients With Chronic Myelomonocytic Leukemia

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01235117
• Other study ID #: CDR0000688119
• Secondary ID: CTRU-CMML-201ISR
• Status: Completed
• Phase: Phase 2
• First received: November 4, 2010
• Last updated: August 23, 2013
• Start date: January 2010
• Est. completion date: May 2013

Study information

• Verified date: November 2010
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: May 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic

Intervention

Drug:
• azacitidine

Other:
• laboratory biomarker analysis

Locations

Country	Name	City	State
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England

Sponsors (1)

Lead Sponsor	Collaborator
University of Leeds

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability			Yes
Primary	Overall response rate			No
Secondary	Incidence of clinical remission/complete remission or partial response according to International Working Group (IWG) criteria			No
Secondary	Hematological improvement according to IWG criteria			No
Secondary	Overall survival			No
Secondary	Progression-free survival			No
Secondary	Time to acute myeloid leukemia (AML) transformation of CMML			No
Secondary	Time to death or AML transformation of CMML			No
Secondary	Biological correlates			No