Imatinib Mesylate With or Without Hydroxychloroquine in Treating Patients With Chronic Myeloid Leukemia

Phase 2

• Conditions: Leukemia

• Registration Number: NCT01227135
• Lead Sponsor: Lynn McMahon

Brief Summary

RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as hydroxychloroquine, may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether imatinib mesylate is more effective when given with or without hydroxychloroquine in treating patients with chronic myeloid leukemia.

PURPOSE: This randomized phase II trial is studying the side effects of giving imatinib mesylate with or without hydroxychloroquine and to see how well it works in treating patients with chronic myeloid leukemia.

Detailed Description

OBJECTIVES:

Primary

* To determine if imatinib mesylate versus hydroxychloroquine (HCQ) and imatinib mesylate is more effective in terms of BCR/ABL levels in patients with chronic myeloid leukemia in major cytogenetic response (MCyR) with residual BCR/ABL-positive cells detectable by quantitative polymerase chain reaction after at least one year of imatinib mesylate treatment.

* To determine the safety and tolerability of this regimen in these patients.

Secondary

* To determine whether the introduction of HCQ influences imatinib mesylate plasma levels.

* To determine if whole blood HCQ levels achieved in combination with imatinib mesylate are in the expected range.

* To determine if HCQ inhibits autophagy in vivo.

* To evaluate the effects of this regimen on residual BCR/ABL-positive primitive progenitors.

OUTLINE: This is a multicenter study. Patients are stratified according to baseline polymerase chain reaction (PCR) level (\< 3 logs below baseline vs ≥ 3 logs below baseline), time on imatinib mesylate (12 to \< 24 months vs 24 to \< 36 months), imatinib mesylate dose (\< 400 mg vs 400 mg to \< 600 mg vs 600 mg to 800 mg), and center. Patients are randomized to 1 of 2 treatment arms.

* Arm A: Patients receive oral imatinib mesylate daily. Treatment repeats every 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity.

* Arm B: Patients receive oral imatinib mesylate daily and oral hydroxychloroquine (HCQ) twice daily. Treatment repeats every 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity.

In both arms, patients may then receive oral imatinib mesylate daily for another 12 months during the follow up period of this study.

Consenting patients undergo blood sample and bone marrow collection at baseline, during, and after completion of study therapy for pharmacologic and other laboratory studies.

After completion of study treatment, patients are followed up at 3, 6, 9, and 12 months.

Peer Reviewed, Funded by MRC and supported by Cancer Research UK

Study Timeline

• Study Start: 2010-03
• Study First Submitted: 2010-10-21
• Study First Submitted QC: 2010-10-22
• Study First Posted: 2010-10-25
• Status Verified: 2011-11
• Last Update Submitted: 2011-11-29
• Last Update Posted: 2011-11-30
• Primary Completion: 2012-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Proportion of treatment "successes" defined as patients who have at least 0.5 log reductions or more in their 12-month PCR level from baseline

Secondary Outcome Measures

Name	Time	Method
Proportion of treatment "successes" at 24 months
Molecular response at 12 and 24 months (complete response, major response, or no response)
Proportion of patients with progression at 12 and 24 months

Trial Locations

Locations (3)

Royal Liverpool University Hospital; 🇬🇧 Liverpool, England, United Kingdom

Imperial College London; 🇬🇧 London, England, United Kingdom

Gartnavel General Hospital; 🇬🇧 Glasgow, Scotland, United Kingdom