in M4/M5 acute myeloid leukemia patients
Thanks to support of the Leukemia and Lymphoma Society (USA), we carried out a Canada-wide Phase II clinical trial to assess the use of Ribavirin as a novel therapy in the treatment of M4/M5 acute myeloid (AML) leukemia patients. This trial stemmed from pre-clinical studies indicating that ribavirin suppresses a cellular factor, eIF4E, which is involved in making cells cancerous.
Our initial findings were exciting, where many patients achieved striking responses including a complete remission lasting nearly 8 months, two partial remissions, and patients with blast responses (reduction in the % of blasts in the bone marrow by 50% or more). There was no ribavirin related toxicities observed in any of our patients. These trial results were published in the journal Blood (Assouline et al., 2009). We followed this with a second trial, combining ribavirin with low-dose Ara-C which also led to exciting clinical responses (Assouline et al, Haematologica, in press). Unfortunately, patients eventually developed resistance to ribavirin in both trials.
We carried out studies to better understand the molecular basis of drug resistance in order to overcome this in our patients (Zahreddine et al., Nature, 2014). We identified a new form of drug resistance, inducible drug modification and found that inhibition of the sonic hedgehog transcription factor repressed this. Thus, in a third trial, we are targeting eIF4E and drug resistance in combination.
The study team is led by Dr Katherine Borden at the Institute for Research in Immunology and Cancer (IRIC) at the Université de Montréal and involves several sites throughout Canada. Dr Sarit Assouline, at the Jewish General Hospital, is in charge of the clinical aspects of the study. The clinical trial is managed from the Clinical Research Unit at the Jewish General Hospital, a McGill affiliated hospital. For more information about the trial, please contact Dr Effie Cocolakis, the study coordinator (firstname.lastname@example.org).