Azacitidine in Treating Patients With Chronic Myelomonocytic Leukemia

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01235117
First received: November 4, 2010
Last updated: August 23, 2013
Last verified: November 2010
  Purpose

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 Intervention Phase
Leukemia
Drug: azacitidine
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Azacitidine in Chronic Myelomonocytic Leukemia (CMML)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety and tolerability [ Designated as safety issue: Yes ]
  • Overall response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of clinical remission/complete remission or partial response according to International Working Group (IWG) criteria [ Designated as safety issue: No ]
  • Hematological improvement according to IWG criteria [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Time to acute myeloid leukemia (AML) transformation of CMML [ Designated as safety issue: No ]
  • Time to death or AML transformation of CMML [ Designated as safety issue: No ]
  • Biological correlates [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: January 2010
Study Completion Date: May 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01235117

Locations
United Kingdom
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom, G12 0YN
Sponsors and Collaborators
University of Leeds
Investigators
Principal Investigator: David T. Bowen, MD Leeds Cancer Centre at St. James's University Hospital
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT01235117     History of Changes
Other Study ID Numbers: CDR0000688119, CTRU-CMML-201, ISRCTN-21428905, EUDRACT-2008-006349-23, LEEDS-HM08/8540, EU-21082
Study First Received: November 4, 2010
Last Updated: August 23, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
chronic myelomonocytic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Bone Marrow Diseases
Hematologic Diseases
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Neoplasms
Neoplasms by Histologic Type
Azacitidine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014