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).
- 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
- To determine the safety and tolerability of this regimen in these patients.
- To determine whether the introduction of HCQ influences imatinib mesylate plasma
- 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
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
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
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
Tessa Holyoake, MD
Gartnavel General Hospital
United Kingdom: Medicines and Healthcare Products Regulatory Agency