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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2011 by University of Glasgow.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Medical Research Council
CRUK Trials unit Glasgow
Information provided by (Responsible Party):
Lynn McMahon, University of Glasgow
ClinicalTrials.gov Identifier:
NCT01227135
First received: October 21, 2010
Last updated: November 29, 2011
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: hydroxychloroquine
Drug: imatinib mesylate
Genetic: cytogenetic analysis
Genetic: polymerase chain reaction
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: CHOICES: A Randomized Phase II Trial of Imatinib (IM) Versus Hydroxychloroquine (HCQ) and IM for Patients With Chronic Myeloid Leukemia (CML) in Major Cytogenetic Response (MCyR) With Residual Disease Detectable by Quantitative Polymerase Chain Reaction (Q-PCR).

Resource links provided by NLM:


Further study details as provided by University of Glasgow:

Primary Outcome Measures:
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of treatment "successes" at 24 months [ Designated as safety issue: No ]
  • Molecular response at 12 and 24 months (complete response, major response, or no response) [ Designated as safety issue: No ]
  • Proportion of patients with progression at 12 and 24 months [ Designated as safety issue: No ]

Estimated Enrollment: 66
Study Start Date: March 2010
Estimated Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of chronic myeloid leukemia (CML) in chronic phase (CP)
  • Has been treated with imatinib mesylate for at least 1 year

    • Receiving a stable dose for ≥ 6 months prior to randomization
  • Achieved at least major cytogenetic response (MCyR) and continues to be BCR/ABL-positive by quantitative polymerase chain reaction (Q-PCR)
  • Must have a fusion gene present that can be monitored by Q-PCR

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm³ (stable and within normal range for ≥ 2 months)
  • Platelet count ≥ 100,000/mm³ (stable and within normal range for ≥ 2 months)
  • Serum albumin > 3 g/dL
  • AST and/or ALT ≤ 2.5 times upper limit of normal (ULN)
  • Serum bilirubin ≤ 1.5 times ULN
  • Serum creatinine ≤ 1.5 times ULN OR 24-hour creatinine clearance ≥ 50 mL/min
  • Serum potassium ≥ lower limit of normal with or without replacement therapy
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-method contraception (including a barrier method [i.e., condom]) during and for 3 months after completion of study therapy
  • No impaired cardiac function, including any of the following:

    • QTc > 450 msec on screening ECG
    • Congenital long QT syndrome
    • History or presence of sustained ventricular tachycardia
    • History of ventricular fibrillation or Torsades de pointes
    • NYHA class III-IV congestive heart failure
    • Uncontrolled hypertension
  • No severe gastrointestinal (GI) disorder, uncontrolled epilepsy, known glucose-6-phosphate dehydrogenase (G6PD) deficiency, known porphyria, moderate or severe psoriasis, known myasthenia gravis, or other concurrent severe and/or uncontrolled medical conditions
  • No preexisting maculopathy of the eye
  • No significant history of noncompliance to medical regimens or the inability to grant a reliable informed consent

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy, investigational drug, or major surgery and recovered
  • More than 6 months since change in imatinib mesylate dose
  • No other concurrent anticancer therapy or radiotherapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01227135

Locations
United Kingdom
Royal Liverpool University Hospital Recruiting
Liverpool, England, United Kingdom, L7 8XP
Contact: Contact Person    44-151-706-4297    r.e.clark@liverpool.ac.uk   
Imperial College London Recruiting
London, England, United Kingdom, W12 0HS
Contact: Contact Person    44-20-8383-1627    d.marin@imperial.ac.uk   
Gartnavel General Hospital Recruiting
Glasgow, Scotland, United Kingdom, G12 0YN
Contact: Contact Person    44-141-301-7881    t.holyoake@clinmed.gla.ac.uk   
Sponsors and Collaborators
Lynn McMahon
Medical Research Council
CRUK Trials unit Glasgow
Investigators
Principal Investigator: Tessa Holyoake, MD Gartnavel General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Lynn McMahon, Project Manager, University of Glasgow
ClinicalTrials.gov Identifier: NCT01227135     History of Changes
Other Study ID Numbers: CDR0000686729, CRUK-H135, ISRCTN-61568166, EUDRACT-2009-014373-41, EU-21078
Study First Received: October 21, 2010
Last Updated: November 29, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Glasgow:
chronic phase chronic myelogenous leukemia
chronic myelogenous leukemia, BCR-ABL1 positive

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Hydroxychloroquine
Imatinib
Anti-Infective Agents
Antimalarials
Antineoplastic Agents
Antiparasitic Agents
Antiprotozoal Agents
Antirheumatic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014