Azacitidine in Treating Patients With Chronic Myelomonocytic Leukemia

August 23, 2013 updated by: University of Leeds

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • England
      • Leeds, England, United Kingdom, LS9 7TF
        • Leeds Cancer Centre at St. James's University Hospital
    • Scotland
      • Glasgow, Scotland, United Kingdom, G12 0YN
        • Beatson West of Scotland Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall response rate
Safety and tolerability

Secondary Outcome Measures

Outcome Measure
Progression-free survival
Overall survival
Incidence of clinical remission/complete remission or partial response according to International Working Group (IWG) criteria
Hematological improvement according to IWG criteria
Time to acute myeloid leukemia (AML) transformation of CMML
Time to death or AML transformation of CMML
Biological correlates

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Leeds

Investigators

  • Principal Investigator: David T. Bowen, MD, Leeds Cancer Centre at St. James's University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

November 4, 2010

First Submitted That Met QC Criteria

November 4, 2010

First Posted (Estimate)

November 5, 2010

Study Record Updates

Last Update Posted (Estimate)

August 26, 2013

Last Update Submitted That Met QC Criteria

August 23, 2013

Last Verified

November 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000688119
  • CTRU-CMML-201
  • ISRCTN-21428905
  • EUDRACT-2008-006349-23
  • LEEDS-HM08/8540
  • EU-21082

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Leukemia

Clinical Trials on laboratory biomarker analysis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Pakistan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe