Treatment of CML Patients With Imatinib and Hydroxyurea (CML2004)

NCT ID: NCT02480608

Last Updated: 2015-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 113 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-04-30
• Study Completion Date: 2013-05-31

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.

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Imatinib

Intervention Type: DRUG

Hydroxyurea

Intervention Type: DRUG

monotherapy Imatinib

Imatinib monotherapy

Group Type: ACTIVE_COMPARATOR

Imatinib

Intervention Type: DRUG

Interventions

Imatinib

Intervention Type: DRUG

Hydroxyurea

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Leipzig

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. med. Thoralf Lange

Prof. Dr. med. Thoralf Lange

Responsibility Role: PRINCIPAL_INVESTIGATOR

References

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.

Reference Type: DERIVED

PMID: 32672489 (View on PubMed)

Other Identifiers

68

Identifier Type: -

Identifier Source: org_study_id