Method of treating leukemia

Abstract

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.