Imatinib Mesylate With or Without Hydroxychloroquine in Treating Patients With Chronic Myeloid Leukemia - Full Text View

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:

MedlinePlus related topics: Cancer Chronic Myeloid Leukemia Leukemia

Drug Information available for: Hydroxychloroquine Hydroxychloroquine sulfate Imatinib Imatinib mesylate

U.S. FDA Resources

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

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:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Hydroxychloroquine
Imatinib
Enzyme Inhibitors

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antineoplastic Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on June 17, 2013