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Clinical Trial
. 2024 Mar;204(3):898-909.
doi: 10.1111/bjh.19193. Epub 2023 Nov 10.

Phase 1/2 study of CPX-351 for patients with Int-2 or high risk International Prognostic Scoring System myelodysplastic syndromes and chronic myelomonocytic leukaemia after failure to hypomethylating agents

Guillermo Montalban-Bravo  1 , Elias Jabbour  1 , Gautam Borthakur  1 , Tapan Kadia  1 , Farhad Ravandi  1 , Kelly Chien  1 , Naveen Pemmaraju  1 , Danielle Hammond  1 , Xiao Qin Dong  1 , Xuelin Huang  2 , Heather Schneider  1 , Rosmy John  1 , Rashmi Kanagal-Shamana  3 , Sanam Loghavi  3 , Hagop Kantarjian  1 , Guillermo Garcia-Manero  1
Affiliations
Clinical Trial

Phase 1/2 study of CPX-351 for patients with Int-2 or high risk International Prognostic Scoring System myelodysplastic syndromes and chronic myelomonocytic leukaemia after failure to hypomethylating agents

Guillermo Montalban-Bravo et al. Br J Haematol. 2024 Mar.

Abstract

Failure after hypomethylating agents (HMAs) is associated with dismal outcomes in higher risk myelodysplastic syndromes (HR-MDS) or chronic myelomonocytic leukaemia (CMML). We aimed to evaluate the safety and preliminary activity of lower doses of CPX-351, a liposomal encapsulation of cytarabine and daunorubicin, in a single-centre, phase 1/2 study for patients with HR-MDS or CMML after HMA failure. Four doses of CPX-351 (10, 25, 50 and 75 units/m2 ) administered on Days 1, 3 and 5 of induction and Days 1 and 3 of consolidation were evaluated. Between June 2019 and June 2023, 25 patients were enrolled (phase 1: n = 15; phase 2: n = 10) including 19 (76%) with HR-MDS and 6 (24%) with CMML. Most common grade 3-4 non-haematological treatment-emergent adverse events were febrile neutropenia (n = 12, 48%) and lung infection (n = 5, 20%). Three patients (age >75) experienced cardiac toxicity at the 75 units/m2 dose. Further enrolment continued at 50 units/m2 . Four- and 8-week mortality were 0% and 8% respectively. The overall response rate was 56% with median relapse-free and overall survivals of 9.2 (95% CI 3.2-15.1 months) and 8.7 months (95% CI 1.8-15.6 months) respectively. These data suggest that lower doses of CPX-351 are safe. Further studies are needed to evaluate its activity.

Trial registration: ClinicalTrials.gov NCT03896269.

Keywords: CMML; MDS; clinical trials; therapy.

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Conflict of interest statement

G.M.-B. declares grant/research support from Takeda, Rigel and IFM Therapeutics. H.K. declares research support from AbbVie, Agios, Amgen, Ariad, Astex, BMS, Cyclacel, Daiichi-Sankyo, Immunogen, Jazz Pharma, Novartis and Pfizer, honoraria from AbbVie, Actinium, Agios, Amgen, Immunogen, Orsinex, Pfizer and Takeda, and an advisory role with Actinium. G.G.-M. declares support from and an advisory role with Celgene Corporation, Astex and Amphivena, and grant/research support 15 from Helsinn, Novartis, AbbVie, Onconova, H3 Biomedicine and Merck. The rest of authors declare no competing financial interests.

References

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