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

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: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Intervention / Treatment: Drug: Hydroxyurea; Drug: Imatinib

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

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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

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	complete molecular response is achieved if BCR-ABL (breakpoint cluster region-Abelson murine leukemia) transcripts became undetectable	18 months

Collaborators and Investigators

• Sponsor: University of Leipzig

Publications and helpful links

General Publications

• 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.

Study record dates

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: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Antisickling Agents; Imatinib Mesylate; Hydroxyurea
• Other Study ID Numbers: 68