Combination treatment for hematological cancers
The present invention relates to a combination treatment for hematological cancers. More specifically; a combination of a telomerase inhibitor and a Bcl-2 inhibitor are useful in treating hematological cancers, including AML. In certain embodiments, the telomerase inhibitor is imetelstat or imetelstat sodium and the Bcl-2 inhibitor is ABT-199.
1. A method of treating acute myeloid leukemia comprising administering imetelstat and ABT-199 to a subject having acute myeloid leukemia, wherein the administration of ABT-199 is one day before, one day after, or the same day as, the administration of imetelstat
wherein imetelstat is administered for 1, 2, 3, 4, 5, 6, 7, 8 or more than 8 dosage cycles, each cycle comprising:
(a) intravenous administration of about 7-10 mg/kg imetelstat once every four weeks;
(b) intravenous administration of about 7-10 mg/kg imetelstat once weekly for four weeks;
(c) intravenous administration of about 2.5-10 mg/kg imetelstat once every three weeks; or
(d) intravenous administration of about 0.5-9.4 mg/kg imetelstat once every four weeks, and
wherein ABT-199 is administered at a dose of:
(a) about 50-400 mg ABT-199 daily;
(b) about 2 mg ABT-199 on day 1 with daily escalation to a final dose of about 800 mg on day 6 and daily thereafter; or
(c) about 25 mg ABT-199 on day 1 with daily escalation to a final dose of about 400 mg on day 5 and daily thereafter.
2. An in vitro method of inducing apoptosis in an acute myeloid leukemia (AML) cell comprising:
contacting the cell with imetelstat sodium at a concentration of 10-75 μM; and
contacting the cell with ABT-199 at a concentration of 5-1000 nM.
3. The method of claim 1 , wherein imetelstat is imetelstat sodium.
4. A method of inducing apoptosis in an acute myeloid leukemia cell comprising contacting the cell with a therapeutically effective amount of imetelstat and contacting the cell with a therapeutically effective amount of ABT-199, wherein the contacting with ABT-199 is one day before, one day after, or the same day as, the contacting with imetelstat
wherein the contacting with imetelstat comprises administration for 1, 2, 3, 4, 5, 6, 7, 8 or more than 8 dosage cycles, each cycle comprising:
(a) intravenous administration of about 7-10 mg/kg imetelstat once every four weeks;
(b) intravenous administration of about 7-10 mg/kg imetelstat once weekly for four weeks;
(c) intravenous administration of about 2.5-10 mg/kg imetelstat once every three weeks; or
(d) intravenous administration of about 0.5-9.4 mg/kg imetelstat once every four weeks, and
wherein the contacting with ABT-199 comprises administration at a dose of:
(a) about 50-400 mg ABT-199 daily;
(b) about 2 mg ABT-199 on day 1 with daily escalation to a final dose of about 800 mg on day 6 and daily thereafter; or
(c) about 25 mg ABT-199 on day 1 with daily escalation to a final dose of about 400 mg on day 5 and daily thereafter.
5. The method of claim 4 , wherein imetelstat is imetelstat sodium.