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

Primary Purpose

Leukemia

Status

Unknown status

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

hydroxychloroquine

imatinib mesylate

cytogenetic analysis

polymerase chain reaction

laboratory biomarker analysis

pharmacological study

About this trial

This is an interventional treatment trial for Leukemia focused on measuring chronic phase chronic myelogenous leukemia, chronic myelogenous leukemia, BCR-ABL1 positive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Royal Liverpool University HospitalRecruiting
Imperial College LondonRecruiting
Gartnavel General HospitalRecruiting

Outcomes

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

Secondary Outcome Measures

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

Full Information

NCT ID

NCT01227135

First Posted

October 21, 2010

Last Updated

November 29, 2011

Sponsor

Lynn McMahon

Collaborators

Medical Research Council, CRUK Trials unit Glasgow

1. Study Identification

Unique Protocol Identification Number

NCT01227135

Brief Title

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

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).

Study Type

Interventional

2. Study Status

Record Verification Date

November 2011

Overall Recruitment Status

Unknown status

Study Start Date

March 2010 (undefined)

Primary Completion Date

March 2012 (Anticipated)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Lynn McMahon

Collaborators

Medical Research Council, CRUK Trials unit Glasgow

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia

Keywords

chronic phase chronic myelogenous leukemia, chronic myelogenous leukemia, BCR-ABL1 positive

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Masking

None (Open Label)

Allocation

Randomized

Enrollment

66 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

hydroxychloroquine

Intervention Type

Drug

Intervention Name(s)

imatinib mesylate

Intervention Type

Genetic

Intervention Name(s)

cytogenetic analysis

Intervention Type

Genetic

Intervention Name(s)

polymerase chain reaction

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Type

Other

Intervention Name(s)

pharmacological study

Primary Outcome Measure Information:

Title

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 Measure Information:

Title

Proportion of treatment "successes" at 24 months

Title

Molecular response at 12 and 24 months (complete response, major response, or no response)

Title

Proportion of patients with progression at 12 and 24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tessa Holyoake, MD

Organizational Affiliation

Gartnavel General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Royal Liverpool University Hospital

City

Liverpool

State/Province

England

ZIP/Postal Code

L7 8XP

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Contact Person

Phone

44-151-706-4297

r.e.clark@liverpool.ac.uk

Facility Name

Imperial College London

City

London

State/Province

England

ZIP/Postal Code

W12 0HS

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Contact Person

Phone

44-20-8383-1627

d.marin@imperial.ac.uk

Facility Name

Gartnavel General Hospital

City

Glasgow

State/Province

Scotland

ZIP/Postal Code

G12 0YN

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Contact Person

Phone

44-141-301-7881

t.holyoake@clinmed.gla.ac.uk

12. IPD Sharing Statement

Learn more about this trial

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

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