Treatment of CML Patients With Imatinib and Hydroxyurea (CML2004) (CML2004)

June 23, 2015 updated by: Prof. Dr. med. Thoralf Lange, University of Leipzig

Treatment of CML Patients With Imatinib and Hydroxyurea

The study will test the tolerability and efficacy of the combination therapy Imatinib/Hydroxyurea (HU) in patients with chronic myeloid leukemia (CML) in first chronic phase (CP1) newly diagnosted or failing interferon-based therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The protocol consists of a part 1, a phase I study that will enrol 20 patients, with the goal to determine the safety of the combination as well as the maximal tolerated dose. If the toxicity of the combination is acceptable, up to 200 more patients may be recruited and randomized to receive either Imatinib/HU or Imatinib alone (part 2).

Patients who meet the inclusion criteria will be started on 400 mg Imatinib daily. In part 1 of the protocol, the dose of HU will be increased by 500 mg at 3-weekly intervals until the maximal tolerated dose has been reached. In part 2 of the study, patients will be randomized to receive either the combination or Imatinib monotherapy.

Hematological and cytogenetic response will be evaluated at 3-months intervals during the first year, and at 6 months' intervals thereafter. Primary endpoints for part 1 are dose-limiting toxicity and maximal tolerated dose. Primary endpoints for part 2 are the rates of major and complete molecular response at 6, 12 and 18 months, respectively.

Study Type

Interventional

Enrollment (Actual)

113

Phase

  • Phase 2
  • Phase 1

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:

  1. Ph-positive CML in CP1, newly diagnosed or resistant (hematologic or cytogenetic) or intolerant to interferon-based therapy
  2. Age ≥ 18 years
  3. Negative pregnancy test
  4. Low- and intermediate risk patients younger than 45 with an HLA (Human Leukocyte Antigen) -matched sibling donor and medically fit to undergo allografting should be included only after they have been adequately counselled about the potential risk (of disease progression) associated with delaying the allograft
  5. Informed consent

Exclusion Criteria:

  1. Objective signs of disease progression beyond CP1 defined as

    • bone marrow or peripheral blood blasts > 15% and/or
    • blasts + promyelocytes ≥ 30% and/or
    • peripheral blood basophils ≥ 20% and/or
    • platelets < 100/nl and/or
    • chromosomal abnormalities in addition to the Ph chromosome
  2. Findings suggestive of extramedullary involvement
  3. Any severe and uncontrolled medical condition
  4. Previous treatment with Imatinib (only part 2 of the study)
  5. History of non-compliance
  6. Simultaneous inclusion in other studies

Important note: previous treatment with Imatinib only is not an exclusion criterion for part 1 of the study.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: combination Imatinib + Hydroxyurea
Patients who meet the inclusion criteria will be started on 400 mg Imatinib daily. In part 1 of the protocol, the dose of HU will be increased by 500 mg at 3-weekly intervals until the maximal tolerated dose has been reached. In part 2 of the study, patients will be randomized to receive either the combination or Imatinib monotherapy.
Drug: Hydroxyurea
Drug: Imatinib
Active Comparator: monotherapy Imatinib
Imatinib monotherapy
Drug: Imatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
number of participants with complete molecular response as a measure of efficacy
Time Frame: 18 months
complete molecular response is achieved if BCR-ABL (breakpoint cluster region-Abelson murine leukemia) transcripts became undetectable
18 months

Collaborators and Investigators

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

Sponsor

University of Leipzig

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

April 1, 2004

Primary Completion (Actual)

August 1, 2011

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

June 10, 2015

First Submitted That Met QC Criteria

June 23, 2015

First Posted (Estimate)

June 24, 2015

Study Record Updates

Last Update Posted (Estimate)

June 24, 2015

Last Update Submitted That Met QC Criteria

June 23, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 68

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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