CHOICES-CHlOroquine and Imatinib Combination to Eliminate Stem cells

• Research type

  Research Study

• Full title

  A randomised Phase II trial of Imatinib (IM) versus Hydroxychloroquine (HCQ) and Imatinib (IM) for patients with Chronic Myeloid Leukaemia (CML) in Cytogenetic Response (CyR) with residual disease detectable by quantitative polymerase chain reaction (Q-PCR)

• IRAS ID

  29975

• Contact name

  Tessa Holyoake

• Sponsor organisation

  NHS Greater Glasgow and Clyde,

• Eudract number

  2009-014373-41

• ISRCTN Number

  ISRCTN61568166

• Research summary

  Chronic myeloid leukaemia (CML) is currently treated with tyrosine kinase inhibitors (TKI), which bind and inhibit the function of BCR/ABL, the abnormal protein found in CML cells. In the majority of cases these drugs convert CML from rapidly progressive and fatal to a chronic condition where quality of life is maintained for at least 10 years on continuous drug therapy. Continuous drug therapy is expensive and associated with significant side effects. Since BCR/ABL is the major survival factor driving CML, when this protein is switched off by TKI the majority of CML cells die. Cells which fail to die in response to these drugs are stem or bone marrow founder cells. It is critical to find ways to kill CML stem cells as these cells re-constitute the disease and without killing these cells CML cannot be cured. Long term aims are to find drugs that can cure CML in early phase and improve responses in advanced phase. When CML cells, including stem cells, are exposed to TKI they induce a process called "autophagy" in which cells break down their own intracellular constituents to produce energy. Producing energy in this way enables cells to survive drug exposure. Preliminary studies have shown that the drug hydroxychloroquine (HCQ), which inhibits "autophagy", potentiates the effect of TKI in inducing death of CML cells, including stem cells. The aim of this study is to lead a trial in which patients who have been on imatinib (standard TKI for CML) for 12 months and are tolerating it well with a partial response to treatment will be randomised to 12 months of treatment with either imatinib alone or imatinib plus HCQ.

• REC name

  West of Scotland REC 1

• REC reference

  09/S0703/112

• Date of REC Opinion

  3 Dec 2009

• REC opinion

  Further Information Favourable Opinion