Evaluation of CPX-351 Monotherapy in Acute Myeloid Leukemia Secondary to Myeloproliferative Neoplasm

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).

Timeline

Start

2022-03-23

Primary completion

2023-10-15

Completion

2023-12-04

Publications

• Background Courtier F, Carbuccia N, Garnier S, Guille A, Adelaide J, Cervera N, Gelsi-Boyer V, Mozziconacci MJ, Rey J, Vey N, Chaffanet M, Birnbaum D, Murati A. Genomic analysis of myeloproliferative neoplasms in chronic and acute phases. Haematologica. 2017 Jan;102(1):e11-e14. doi: 10.3324/haematol.2016.152363. Epub 2016 Oct 14. No abstract available.
• Background Luque Paz D, Jouanneau-Courville R, Riou J, et al. Leukemic evolution of polycythemia vera and essential thrombocythemia: genomic profiles predict time to transformation. Blood Adv. 2020;4(19):4887-4897. Blood Adv. 2020 Nov 24;4(22):5651. doi: 10.1182/bloodadvances.2020003711. No abstract available.

Drugs

Indications