Study Design of an Expanded Access Protocol of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection in Patients 60-75 Years of Age with Secondary Acute Myeloid Leukemia

Introduction: Intensive induction chemotherapy for acute myeloid leukemia (AML) in patients aged 60 years or older has lower remission rates with increased induction mortality compared with younger patients; however, long-term remission has been reported in AML patients of all ages after allogeneic transplantation. CPX-351 is a liposomal formulation of cytarabine and daunorubicin encapsulated at a 5:1 molar ratio. In Phase II and III randomized trials in newly diagnosed older patients with secondary AML, results demonstrated survival benefit for patients treated with CPX-351 versus standard 7 + 3 cytarabine and daunorubicin (Figure 1). Further, exploratory results from the Phase III trial suggest that CPX-351 may provide a more effective bridge to transplant for this very poor-risk subgroup of AML patients. A new expanded access protocol (NCT02533115) designed to provide access to CPX-351 and collect safety and some efficacy data has been initiated. Methods: This expanded access protocol is a Phase IV multicenter, single-arm, open-label study in patients with secondary AML who are suitable for treatment with intensive chemotherapy. After providing informed consent and undergoing pretreatment evaluations, patients may receive ≤2 inductions and ≤4 consolidation courses. Consolidation with allogeneic transplant is permitted. Patients will be monitored for serious and grade 3-5 adverse events. This protocol is being conducted in accordance with the Declaration of Helsinki. Eligibility criteria are similar to the Phase III trial: Patients aged 60 to 75 years with newly diagnosed secondary AML defined as having a history of prior cytotoxic treatment, antecedent myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (±prior treatment with hypomethylating agents), or AML with World Health Organization–defined MDS-related cytogenetic abnormalities. Treatment is CPX-351 induction (100 units/m2 [100 mg/m2 cytarabine + 44 mg/m2 daunorubicin] on days 1, 3, and 5 [first induction only]) and consolidation (65 units/m2 on days 1 and 3). Patients unable to achieve a complete response (CR) or CR with incomplete platelet or neutrophil recovery (CRi) after 2 inductions should be discontinued from the study. Results: Enrollment was recently initiated with 17 patients at the first 6 sites in the United States, and is ongoing. Conclusions: This Phase IV protocol is designed to provide access to CPX-351 to patients 60-75 years of age with newly diagnosed secondary AML meeting the general eligibility criteria for the Phase III study. Support: Celator Pharmaceuticals, Inc., a subsidiary of Jazz Pharmaceuticals plc.