Assays and methods for selecting a treatment regimen for a subject with leukemia
Diagnostic methods for identifying cancer bearing subjects appropriate for treatment with CPX-351 include genetic and ex vivo testing of cells from a candidate subject. Combination treatment with CPX-351 and FLT-3 inhibitors improve CPX-351 uptake and toxicity.
1. A method to treat a hematologic cancer in a hematologic cancer-bearing subject which method consists essentially of administering an effective amount of a combination of an inhibitor of Fms-like tyrosine receptor kinase 3 (FLT 3) and a liposomal formulation comprising cytarabine and daunorubicin co-encapsulated at a synergistic molar ratio.
2. The method of claim 1 , wherein said subject has a mutation in the Fms-like tyrosine receptor kinase 3 (FLT 3) gene.
3. The method of claim 1 , wherein the mutation is an activating mutation in the FLT 3 gene.
4. The method of claim 1 , wherein the FLT-3 inhibitor and the liposomal formulation are administered simultaneously or wherein the liposomal formulation is administered prior to treatment with FLT-3 inhibitor or wherein the FLT-3 inhibitor and the liposomal formulation are administered in the same composition.
5. The method of claim 1 , wherein the hematologic cancer is selected from the group consisting of acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CIVIL), myeloproliferative neoplasms (MPNs) and lymphomas.
6. The method of claim 1 , wherein the FLT-3 inhibitor is quizartinib, midostaurin, tandutinib, sorafenib, sunitinib, lestaurtinib, crenolanib, gilteritinib, AST-487, dovitinib or linifanib.
7. The method of claim 1 , wherein the liposomal formulation is a low-cholesterol liposomal formulation.
8. The method of claim 1 , wherein the liposomal formulation comprises cytarabine and daunorubicin co-encapsulated at a 5:1 molar ratio.