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. The method of claim 1 , wherein the subject received and failed all known effective therapies for the hematological cancer.
3. 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.
4. The method of claim 1 , wherein the hematological cancer is leukemia.
5. The method of claim 4 , wherein the subject has a leukemia characterized by MLL gene rearrangement.
6. The method of claim 5 , wherein the MLL gene rearrangement is translocation of the MLL gene at 11q23.
7. The method of claim 5 , wherein the MLL gene rearrangement is a partial tandem duplication of the MLL gene.
8. 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.
9. The method of claim 8 , wherein the another therapy is standard of care for the treatment of acute myeloid leukemia.
10. The method of claim 8 , wherein the another therapy is standard of care for the treatment of acute lymphoblastic leukemia.
11. 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.
12. The method of claim 11 , wherein the subject received and failed all known effective therapies for the hematological cancer.
13. The method of claim 11 , 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.
14. The method of claim 11 , wherein the hematological cancer is leukemia.
15. The method of claim 14 , wherein the subject has a leukemia characterized by MLL gene rearrangement.
16. The method of claim 15 , wherein the MLL gene rearrangement is translocation of the MLL gene at 11q23 or a partial tandem duplication of the MLL gene.
17. The method of claim 11 , 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.
18. The method of claim 17 , wherein the another therapy is standard of care for the treatment of acute myeloid leukemia.
19. The method of claim 17 , wherein the another therapy is standard of care for the treatment of acute lymphoblastic leukemia.
20. 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.