Evaluation of CPX-351 Monotherapy in Acute Myeloid Leukemia Secondary to Myeloproliferative Neoplasm
Status:
Not yet recruiting
Trial end date:
2025-07-01
Target enrollment:
Participant gender:
Summary
The three classic myeloproliferative neoplasms (MPNs) include polycythemia Vera (PV),
essential thrombocythemia (ET) and primary myelofibrosis (PMF). The natural history of these
MPNs is the possible progression to acute myeloid leukemia (MPN-blast phase) at variable
percentage depending the entity. Leukemic transformation of MPN occurs in 8% to 23% of
primary myelofibrosis (PMF) patients in the first 10 years after diagnosis and in 4% to 8% of
polycythemia vera (PV) and essential thrombocytosis (ET) patients within 18 years after
diagnosis. The risk for leukemic transformation is increased by exposure to cytotoxic
chemotherapy. The molecular pathogenesis of MPN-blast phase remains an area of active
research.
The prognosis of blast phase MPNs is very poor : approximately 50% of the patients are deemed
eligible for intensive treatment (ie. conventional induction chemotherapy regimen with
anthracyclines and cytarabine). The patients who are not fit for such intensive treatment
approach due to age or comorbidities, are treated with Hypomethylating agents, low dose
palliative chemotherapy, or supportive care. Nevertheless, there is a need for more effective
and better tolerated treatment approaches in order to increase the response rate and hence,
the transplant rates which should translate into improved survival.
CPX-351 is a new formulation of cytarabine and daunorubicin encapsulated at a fixed 5:1
molar-ratio in liposomes that exploits molar ratio-dependent drug-drug synergy to enhance
antileukemic efficacy.
Based on similarities between post-myelodysplastic syndrome (MDS) and post-MPN secondary AML
in terms of disease resistance to chemotherapy, of fragile patient profile, The hypotheses
made is that CPX-351 may improve the results of induction chemotherapy without increasing its
toxicity and therefore may increase the proportion of patients who could benefit from an
allogeneic Stem Cell Transplantation (SCT).
Phase:
Phase 2
Details
Lead Sponsor:
French Innovative Leukemia Organisation
Collaborators:
Acute Leukemia French Association French Intergroup of Myeloproliferative syndromes