Imatinib Mesylate With or Without Hydroxychloroquine in Treating Patients With Chronic Myeloid Leukemia
NCT ID: NCT01227135
Last Updated: 2011-11-30
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE2
66 participants
INTERVENTIONAL
2010-03-31
Brief Summary
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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
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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
Conditions
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Keywords
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Study Design
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RANDOMIZED
TREATMENT
NONE
Interventions
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hydroxychloroquine
imatinib mesylate
cytogenetic analysis
polymerase chain reaction
laboratory biomarker analysis
pharmacological study
Eligibility Criteria
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Inclusion Criteria
* 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
18 Years
ALL
No
Sponsors
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Medical Research Council
OTHER_GOV
CRUK Trials unit Glasgow
UNKNOWN
Lynn McMahon
OTHER
Responsible Party
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Lynn McMahon
Project Manager
Principal Investigators
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Tessa Holyoake, MD
Role: PRINCIPAL_INVESTIGATOR
Gartnavel General Hospital
Locations
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Royal Liverpool University Hospital
Liverpool, England, United Kingdom
Imperial College London
London, England, United Kingdom
Gartnavel General Hospital
Glasgow, Scotland, United Kingdom
Countries
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Facility Contacts
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Contact Person
Role: primary
Contact Person
Role: primary
Contact Person
Role: primary
Other Identifiers
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CRUK-H135
Identifier Type: -
Identifier Source: secondary_id
ISRCTN-61568166
Identifier Type: -
Identifier Source: secondary_id
EUDRACT-2009-014373-41
Identifier Type: -
Identifier Source: secondary_id
EU-21078
Identifier Type: -
Identifier Source: secondary_id
CDR0000686729
Identifier Type: -
Identifier Source: org_study_id