LOW-INTENSITY TREATMENT OF HEMATOLOGICAL DISORDERS
The invention relates to compositions and methods for treating patients with hematological proliferative disorders who are ineligible for treatment with standard intensive chemotherapy, using low intensity treatment with CPX-351, a liposomal composition of daunorubicin and cytarabine.
1 . A pharmaceutical composition comprising CPX-351 as the sole active ingredient that supplies daunorubicin and cytarabine for use in a treatment cycle to treat a hematological proliferative disorder in a subject ineligible for standard intensive chemotherapy (an ISICT subject), which treatment cycle comprises administering said composition to deliver less than 300 mg/m 2 of cytarabine over the course of the treatment cycle.
2 . The composition of claim 1 wherein said treatment delivers less than 250 mg/m 2 of cytarabine over the course of the treatment cycle.
3 . The composition of claim 1 wherein said treatment cycle delivers daily dose(s) of less than or equal to 135 mg/m 2 per day of cytarabine and consists of 2 days.
4 . The composition of claim 1 wherein said composition is administered for no more than a total of 2 days at intervals of days 1 and 3 or days 1 and 5 or days 1 and 8.
5 . The composition of claim 1 wherein said composition delivers daily dosages of less than 32 mg/m 2 per day of cytarabine and the treatment cycle consists of 3 days or less.
6 . The composition of claim 1 that is administered intravenously in less than 3 hours.
7 . The composition of claim 1 wherein the protocol further includes administering an agent that has been shown effective to treat a leukemia.
8 . The composition of claim 7 wherein said agent is a BCL-2 inhibitor or a hypomethylation agent.
9 . The composition of claim 7 wherein said agent is mylotarg, midostaurin, venetoclax or idhifa.
10 . The composition of claim 1 wherein the hematologic proliferative disorder is acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL) or acute promyelocytic leukemia (APL), myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN).
11 . The composition of claim 7 wherein the hematologic proliferative disorder is AML, ALL, CLL, APL, MDS or MPN.
12 . A method to treat a hematologic proliferative disorder in an ISICT subject, which method comprises administering to said subject a pharmaceutical composition comprising CPX-351 as the sole active ingredient that supplies daunorubicin and cytarabine in a treatment cycle that comprises delivering less than 300 mg/m 2 of cytarabine over the course of the treatment cycle.
13 . The method of claim 12 wherein said treatment delivers less than 250 mg/m 2 of cytarabine over the course of the treatment cycle.
14 . The method of claim 12 wherein said treatment cycle delivers daily dose(s) of less than or equal to 135 mg/m 2 per day of cytarabine and consists of 2 days.
15 . The method of claim 12 wherein said composition is administered for no more than a total of 2 days at intervals of days 1 and 3 or days 1 and 5 or days 1 and 8.
16 . The method of claim 12 said composition delivers daily dosages of less than 32 mg/m 2 per day of cytarabine and the treatment cycle consists of 3 days or less.
17 . The method of claim 12 wherein the composition is administered intravenously in less than 3 hours.
18 . The method of claim 12 wherein the protocol further includes administering an agent that has been shown effective to treat a leukemia.
19 . The method of claim 12 wherein the hematologic proliferative disorder is acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL) or acute promyelocytic leukemia (APL), myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN).
20 . The method of claim 18 wherein the hematologic proliferative disorder is acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL) or acute promyelocytic leukemia (APL), myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN).