Imatinib (Gleevec(Registered Trademark)) to Treat Chronic Myelomonocytic Leukemia and Atypical Chronic Myelogenous Leukemia

June 30, 2017 updated by: National Heart, Lung, and Blood Institute (NHLBI)

A Pilot Study of the Safety and Efficacy of Imatinib in Reducing Monocytosis or Leukocytosis in Patients With Chronic Myelomonocytic Leukemia and Atypical Chronic Myelogenous Leukemia, Respectively

This study will evaluate the safety and effectiveness of imatinib (Gleevec(Registered Trademark)) in patients with chronic myelomonocytic leukemia (CMML) and atypical chronic myelogenous leukemia (CML). These conditions cause uncontrolled growth of malignant (cancerous) cells in the bone marrow that prevents the bone marrow from functioning normally in producing blood cells. The cancer cells also can spill over into the blood and invade other organs of the body. Imatinib has been approved by the Food and Drug Administration for treating chronic myelogenous leukemia, which has characteristics similar to atypical CML and to CMML, and data from other research suggests this drug may be able to produce a remission in forms of leukemia other than CML.

Patients over 18 years of age with atypical CML or CMML may be eligible for this study. Candidates are screened with a medical history and physical examination, blood tests, electrocardiogram, chest x-ray, and bone marrow aspiration and biopsy (removal of a small piece of bone marrow tissue through a needle inserted into the hip bone).

Participants take imatinib capsules once a day for 2 years. If at any time during the study the patient's blood counts begin to rise, disease symptoms develop, or the disease has progressed, the dose of imatinib is increased each week until the disease progression is stopped. Any patient whose disease does not response to treatment after 6 weeks of increased dosing and 30 days at the maximum daily dose of 800 mg is taken off the study and referred for different treatment.

Patients are seen by their referring physician every week for the first 4 weeks of the study, every other week for the next 8 weeks, and then monthly until the study is completed. At each visit, blood is drawn to monitor for drug side effects and response to therapy. In addition, patients come to the NIH Clinical Center every 3 months for a complete history and physical examination and for a bone marrow aspiration and biopsy every 6 months to assess the effect of treatment on bone marrow cells.

Patients who leave the study before 2 years are followed with laboratory monitoring for 6 months after stopping imatinib; those who remain on the drug for the full 2 years are monitored for 1 year after stopping the drug.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to evaluate the safety and effectiveness of imatinib for improving blood counts in patients with chronic myelomonocytic leukemia (CMML) and atypical chronic myelogenous leukemia (CML).

Although a number of agents have been used to treat these diseases, most patients do not respond to treatment. Imatinib has been shown in clinical trials to induce high rates of responses in patients with chronic phase CML. Imatinib has also been shown to be effective in inducing responses in a subset of patients with CMML and atypical CML and is also effective in a subset of patients with idiopathic hypereosinophilic syndrome (HES), another myeloproliferative disorder. Because patients with several different myeloproliferative diseases have been shown to experience dramatic responses to imatinib, we would like to determine what proportion of patients with atypical myeloproliferative diseases (CMML and atypical CML) will respond to this agent.

Prior to enrollment, a thorough clinical evaluation will be performed. A baseline bone marrow will be obtained to exclude acute leukemia or lymphoma and to assess the degree and nature of the myeloproliferation. In order to minimize bone marrow suppression, other myelosuppressive drugs will be tapered and discontinued during the first week of therapy with imatinib. Complete blood counts will be performed weekly for the first month and every other week thereafter. Clinical assessments will be performed every three months to assess for continued response.

Study Type

Interventional

Enrollment (Actual)

7

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 States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

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

  • INCLUSION CRITERIA:

All subjects must be greater than or equal to 18 years of age.

All subjects must meet the established diagnostic criteria for CMML or atypical CML.

The diagnostic criteria for CMML include:

  • persistent peripheral blood monocytosis (greater than 1000/mm(3)),
  • no Philadelphia chromosome or BCR/ABL fusion gene,
  • fewer than 20% blasts in the blood and bone marrow, and
  • dysplasia in one or more myeloid lineages. If dysplasia is absent the diagnosis of CMML can still be made if the other requirements are met and a cytogenetic abnormality is present in the marrow cells or if monocytosis has been persistent for at least 3 months and all other causes of monocytosis have been excluded.

OR

The diagnostic criteria for atypical CML include:

  • peripheral blood leukocytosis comprised of increased mature and immature neutrophils,
  • prominent dysgranulopoiesis,
  • no Philadelphia chromosome or BCR/ABL fusion gene,
  • neutrophil precursors greater than or equal to 10% of white blood cells,
  • basophils less than 2% of white blood cells,
  • monocytes less than 10% of white blood cells,
  • hypercellular bone marrow with granulocytic proliferation and dysplasia, and fewer than 20% blasts in the blood and bone marrow.
  • Serum creatinine less than 2mg/dl
  • ECOG performance status less than 3
  • Life expectancy greater than 12 weeks
  • All subjects (men and women) must agree to practice abstinence or effective contraception during administration of imatinib.
  • Patients must be able to comprehend the investigational nature of the research and be willing to sign an informed consent.

EXCLUSION CRITERIA:

Pregnancy or lactation.

HIV positivity or other known immunodeficiency.

Absolute neutrophil count less than 1000/mm(3) or platelet count less than 10,000/mm(3) or less than 50,000/m(3) with clinical evidence of bleeding.

Infection not adequately responding to appropriate therapy

History of non-hematologic malignancy treated with chemotherapy in past 5 years.

A moribund status or concurrent hepatic, renal, cardiac, metabolic disease of such severity that death within 12 weeks from initiation of therapy is likely.

Treatment with investigational agent (other than hematopoietic growth factors) within 4 weeks of study entry.

Psychiatric, affective, or other disorder that may compromise the ability to give informed consent or to cooperate in a research study.

Elevated transaminases (greater than 5 times the upper limit of normal) or elevated bilirubin (greater than 3 times the upper limit of normal).

Recent exposure to chickenpox or recent history of Herpes zoster (shingles) reactivation. Imatinib may put patients at increased risk of severe disease.

Left ventricular ejection fraction less than 45%.

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
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Peripheral blood absolute monocyte/leukocyte count measured at 2 months.
Time Frame: 2-months
2-months

Secondary Outcome Measures

Outcome Measure
Resolution of bone marrow abnormalities, improvement in transfusion requirements, reduction or disappearance of cytogenetic abnormalities or fusion transcripts as detected by quantitative PCR/progression of clinical disease at 2 mths and every 3...

Collaborators and Investigators

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

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 14, 2004

Primary Completion (Actual)

December 30, 2006

Study Completion (Actual)

October 25, 2010

Study Registration Dates

First Submitted

March 8, 2004

First Submitted That Met QC Criteria

March 9, 2004

First Posted (Estimate)

March 10, 2004

Study Record Updates

Last Update Posted (Actual)

July 2, 2017

Last Update Submitted That Met QC Criteria

June 30, 2017

Last Verified

September 23, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 040090
  • 04-H-0090

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.

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