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

November 29, 2011 updated by: Lynn McMahon

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).

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
66

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • England
      • Liverpool, England, United Kingdom, L7 8XP
        • Recruiting
        • Royal Liverpool University Hospital
        • Contact:
      • London, England, United Kingdom, W12 0HS
        • Recruiting
        • Imperial College London
        • Contact:
    • Scotland
      • Glasgow, Scotland, United Kingdom, G12 0YN

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Lynn McMahon

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Medical Research Council
CRUK Trials unit Glasgow

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Tessa Holyoake, MD, Gartnavel General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2010

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 21, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 22, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 25, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 30, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 29, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CDR0000686729
  • CRUK-H135
  • ISRCTN-61568166
  • EUDRACT-2009-014373-41
  • EU-21078

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Leukemia

Clinical Trials on pharmacological study

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings