Leukemia, Myeloid, Chronic-Phase Clinical Trial
Official title:
A Safety and Efficacy Study of Adding Low Dose Pegylated IFN-alpha 2B to Standard Dose Dasatinib in Patients With Newly Diagnosed Chronic Phase Myeloid Leukemia
Patients with newly diagnosed CML have excellent outcomes with tyrosine kinase inhibitors
(TKI). However, a few patients will be cured with TKIs alone, and thus need continued
life-long treatment. Some patients achieve complete molecular remission (CMR), and this rate
is higher with second generation TKIs compared with imatinib. Some experience with drug
discontinuation in CMR has been derived from a few small studies, most notably the French
STIM study. Approximately 40 % of patients with a minimum of two years in MR4.5 (4.5 log
reduction in molecular response) can stop imatinib without relapse, indicating possible cure.
To increase the non-relapse rate is of major importance. To achieve a permanent "cure"
without stem cell transplantation is presently the most relevant goal of clinical studies in
CML.
The investigators hypothesize that to significantly increase cure rates in CML, therapy
should eradicate leukemic stem cells and/or induce or restore anti-CML immunity. Second
generation TKIs may have a more profound effect on the stem cell pool as compared to
imatinib. This is assessed in our current randomized study with a reduction in leukemic stem
cell burden as the primary endpoint (NordCML006). Interferon-alpha (IFN) has a prominent
immunomodulatory and antiproliferative mode of action, and has also activity in stem cells.
Pegylated IFN in combination with imatinib results in improved therapy responses as compared
to imatinib monotherapy. This advantage may translate into higher cure rates.
Dasatinib has a unique dual mechanism of action: it is the most potent of available TKIs and
induces immunological effects that are different from those of IFN. Both of these drugs may
have immunological adverse-effects when used as a monotherapy. However, immunological
adverse-effects may also be markers of anti-leukemia efficacy. A combination of dasatinib and
pegylated IFN (PegIFN) may have additive or synergistic effects and should be tested in a
clinical study.
n/a
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