CPX-351 and Ivosidenib for the Treatment of IDH1 Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

Summary

Participation Requirements

Description

PRIMARY OBJECTIVE: I. To determine the overall response rate (ORR) including complete remission (CR), complete remission with hematologic recovery (CRh), complete remission with incomplete blood count recovery (CRi), morphologic leukemia-free state (MLFS), and partial remission (PR) of the combinati...

PRIMARY OBJECTIVE: I. To determine the overall response rate (ORR) including complete remission (CR), complete remission with hematologic recovery (CRh), complete remission with incomplete blood count recovery (CRi), morphologic leukemia-free state (MLFS), and partial remission (PR) of the combination of liposome-encapsulated daunorubicin-cytarabine (CPX-351) and ivosidenib in IDH1-mutated patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). SECONDARY OBJECTIVES: I. To assess safety of CPX-351 in combination with ivosidenib. II. To determine time to event endpoints including duration of response (DOR), event free survival (EFS) and overall survival (OS). EXPLORATORY OBJECTIVES: I. Evaluate minimal residual disease (MRD) using multiparameter flow cytometry, cytogenetics and molecular evaluation. II. To evaluate molecular and cellular biomarkers that may be predictive of antitumor activity and/or resistance to treatment including evaluation of 2HG, IDH1 and other co-occurring mutations and VAF levels before, during and after treatment. OUTLINE: INDUCTION: Patients receive CPX-351 intravenously (IV) over 90 minutes on days 1, 3, and 5, and ivosidenib orally (PO) once daily (QD) on days 1-28. Patients who do not achieve complete remission may receive a second cycle of induction therapy in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission proceed to consolidation. CONSOLIDATION: Patients receive CPX-351 IV over 90 minutes on days 1 and 3, and ivosidenib PO QD on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive ivosidenib PO QD for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients who are experiencing clinical benefit and who have not experienced excessive toxicity after completion of 2 years of maintenance may be eligible to continue therapy after discussion with the principal investigator. After completion of study treatment, patients are followed up at 30 days, then monthly for 3 years.

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