search
Back to results

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

Primary Purpose

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Imatinib
Hydroxyurea
Sponsored by
University of Leipzig
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    combination Imatinib + Hydroxyurea

    monotherapy Imatinib

    Arm Description

    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.

    Imatinib monotherapy

    Outcomes

    Primary Outcome Measures

    number of participants with complete molecular response as a measure of efficacy
    complete molecular response is achieved if BCR-ABL (breakpoint cluster region-Abelson murine leukemia) transcripts became undetectable

    Secondary Outcome Measures

    Full Information

    First Posted
    June 10, 2015
    Last Updated
    June 23, 2015
    Sponsor
    University of Leipzig
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT02480608
    Brief Title
    Treatment of CML Patients With Imatinib and Hydroxyurea (CML2004)
    Acronym
    CML2004
    Official Title
    Treatment of CML Patients With Imatinib and Hydroxyurea
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    April 2004 (undefined)
    Primary Completion Date
    August 2011 (Actual)
    Study Completion Date
    May 2013 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Leipzig

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Leukemia, Myelogenous, Chronic, BCR-ABL Positive

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    113 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    combination Imatinib + Hydroxyurea
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    monotherapy Imatinib
    Arm Type
    Active Comparator
    Arm Description
    Imatinib monotherapy
    Intervention Type
    Drug
    Intervention Name(s)
    Imatinib
    Intervention Type
    Drug
    Intervention Name(s)
    Hydroxyurea
    Primary Outcome Measure Information:
    Title
    number of participants with complete molecular response as a measure of efficacy
    Description
    complete molecular response is achieved if BCR-ABL (breakpoint cluster region-Abelson murine leukemia) transcripts became undetectable
    Time Frame
    18 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Ph-positive CML in CP1, newly diagnosed or resistant (hematologic or cytogenetic) or intolerant to interferon-based therapy Age ≥ 18 years Negative pregnancy test 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 Informed consent Exclusion Criteria: 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 Findings suggestive of extramedullary involvement Any severe and uncontrolled medical condition Previous treatment with Imatinib (only part 2 of the study) History of non-compliance Simultaneous inclusion in other studies Important note: previous treatment with Imatinib only is not an exclusion criterion for part 1 of the study.

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    32672489
    Citation
    Lange T, Niederwieser C, Gil A, Krahl R, von Grunhagen U, Al-Ali HK, Jentsch-Ullrich K, Spohn C, Lakner V, Assmann M, Junghanss C, Cross M, Hehlmann R, Deininger M, Pfirrmann M, Niederwieser D. No advantage of Imatinib in combination with hydroxyurea over Imatinib monotherapy: a study of the East German Study Group (OSHO) and the German CML study group. Leuk Lymphoma. 2020 Dec;61(12):2821-2830. doi: 10.1080/10428194.2020.1786556. Epub 2020 Jul 16.
    Results Reference
    derived

    Learn more about this trial

    Treatment of CML Patients With Imatinib and Hydroxyurea (CML2004)

    We'll reach out to this number within 24 hrs