Azacitidine in Treating Patients With Chronic Myelomonocytic Leukemia

Sponsor

University of Leeds (Other)

Overall Status

Completed

CT.gov ID

NCT01235117

Collaborator

(none)

Enrollment

Locations

Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: azacitidine Other: laboratory biomarker analysis	Phase 2

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Non-Randomized

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2010

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

May 1, 2013

Outcome Measures

Primary Outcome Measures

Safety and tolerability []
Overall response rate []

Secondary Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Leeds Cancer Centre at St. James's University Hospital	Leeds	England	United Kingdom	LS9 7TF
2	Beatson West of Scotland Cancer Centre	Glasgow	Scotland	United Kingdom	G12 0YN