LeukemiaPhase 2NCT01227135
Imatinib Mesylate With or Without Hydroxychloroquine in Treating Patients With Chronic Myeloid Leukemia
A Phase 2 study testing hydroxychloroquine, imatinib mesylate and cytogenetic analysis in people with Leukemia, run by Lynn McMahon at 3 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia
- What is being tested?
- hydroxychloroquine, imatinib mesylate and cytogenetic analysis
- How many people
- 66 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Mar 2010to Mar 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites, 3 recruiting
- Recruiting
Gartnavel General Hospital
Glasgow, Scotland, G12 0YN
Contact Person, 44-141-301-7881, t.holyoake@clinmed.gla.ac.uk
- Recruiting
Royal Liverpool University Hospital
Liverpool, England, L7 8XP
Contact Person, 44-151-706-4297, r.e.clark@liverpool.ac.uk
- Recruiting
Imperial College London
London, England, W12 0HS
Contact Person, 44-20-8383-1627, d.marin@imperial.ac.uk
About this study
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).
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.
Read the 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
- Conditions
- Leukemia
- Being tested
- hydroxychloroquine, imatinib mesylate, cytogenetic analysis, polymerase chain reaction, laboratory biomarker analysis
- Keywords
- chronic phase chronic myelogenous leukemia, chronic myelogenous leukemia, BCR-ABL1 positive
- Medical subject headings
- Leukemia, Leukemia, Myeloid, Chronic-Phase, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
imatinib mesylateDrug
cytogenetic analysisGenetic
polymerase chain reactionGenetic
laboratory biomarker analysisOther
What is being measured
The primary outcome is the main question the study is designed to answer.
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 outcomes (3)
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2010 (estimated)
- Study startMar 2010
- Primary completionMar 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lynn McMahon
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council, CRUK Trials unit Glasgow
- Responsible party
- Sponsor-investigator, Lynn McMahon, University of Glasgow
- Investigators
- Tessa Holyoake, MD, Principal investigator, Gartnavel General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01227135
- Sponsor's protocol ID
- CDR0000686729
- Other IDs
- CRUK-H135, ISRCTN-61568166, EUDRACT-2009-014373-41, EU-21078
- Status last verified
- Nov 2011
- First submitted
- 21 Oct 2010
- Last updated
- 30 Nov 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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).
- ClinicalTrials.gov ID
- NCT01227135
- Acronym / sponsor ID
- CDR0000686729
- Conditions
- Leukemia
- Keywords
- chronic phase chronic myelogenous leukemia, chronic myelogenous leukemia, BCR-ABL1 positive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- Lynn McMahonUniversity, hospital or other
- Collaborators
- Medical Research Council, CRUK Trials unit Glasgow
- Study start
- Mar 2010
- Primary completion
- Mar 2012 (estimated)
- First posted
- 25 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hydroxychloroquine | Drug | – |
| imatinib mesylate | Drug | – |
| cytogenetic analysis | Genetic | – |
| polymerase chain reaction | Genetic | – |
| laboratory biomarker analysis | Other | – |
| pharmacological study | Other | – |
Primary outcome
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
3 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Royal Liverpool University Hospital
Liverpool, United Kingdom
Tessa Holyoake, MD principal investigator
Gartnavel General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing hydroxychloroquine, imatinib mesylate and cytogenetic analysis in people with Leukemia, run by Lynn McMahon at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary 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. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2011.