METHOD OF TREATING LEUKEMIA
The present invention relates to methods of treating disorders in which DOT1L-mediated protein methylation plays a part, such as cancer, by administering DOT1L inhibitor compounds and pharmaceutical compositions to subjects in need thereof.
1 . A method for treating a hematological cancer comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I) or its N-oxide or a pharmaceutically acceptable salt thereof:
wherein the subject had at least one prior therapy to treat a hematological cancer and wherein the hematological cancer is refractory to at least one of the prior therapies.
2 . (canceled)
3 . A method for treating a hematological cancer comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I) or its N-oxide or a pharmaceutically acceptable salt thereof:
wherein the subject had at least one prior therapy to treat a hematological cancer and wherein the hematological cancer shows recurrence following remission.
4 . The method of claim 1 , wherein the subject received and failed all known effective therapies for the hematological cancer.
5 . The method of claim 1 , wherein the hematological cancer is selected from the group consisting of acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, a myeloproliferative disorder, and chronic myelogenous leukemia.
6 . The method of claim 1 , wherein the hematological cancer is leukemia.
7 . The method of claim 6 , wherein the subject has a leukemia characterized by MLL gene rearrangement.
8 . The method of claim 7 , wherein the MLL gene rearrangement is translocation of the MLL gene at 11q23.
9 . The method of claim 7 , wherein the MLL gene rearrangement is a partial tandem duplication of the MLL gene.
10 . A method for treating a hematological cancer comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I) or its N-oxide or a pharmaceutically acceptable salt thereof:
wherein the subject is unable to receive other therapy to treat the cancer due to age or intercurrent illness and wherein the hematological cancer is refractory to a prior therapy or the hematological cancer shows recurrence following remission.
11 . The method of claim 1 , wherein the subject is simultaneously being treated with another therapy to treat acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, a myeloproliferative disorder, or chronic myelogenous leukemia.
12 . The method of claim 11 , wherein the another therapy is standard of care for the treatment of acute myeloid leukemia.
13 . The method of claim 11 , wherein the another therapy is standard of care for the treatment of acute lymphoblastic leukemia.
14 . The method of claim 3 , wherein the subject received and failed all known effective therapies for the hematological cancer.
15 . The method of claim 3 , wherein the hematological cancer is selected from the group consisting of acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, a myeloproliferative disorder, and chronic myelogenous leukemia.
16 . The method of claim 3 , wherein the hematological cancer is leukemia.
17 . The method of claim 16 , wherein the subject has a leukemia characterized by MLL gene rearrangement.
18 . The method of claim 17 , wherein the MLL gene rearrangement is translocation of the MLL gene at 11q23 or a partial tandem duplication of the MLL gene.
19 . The method of claim 3 , wherein the subject is simultaneously being treated with another therapy to treat acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, a myeloproliferative disorder, or chronic myelogenous leukemia.
20 . The method of claim 19 , wherein the another therapy is standard of care for the treatment of acute myeloid leukemia.
21 . The method of claim 19 , wherein the another therapy is standard of care for the treatment of acute lymphoblastic leukemia.