Treatment of cancer

Abstract

Provided herein are compositions and methods for the treatment of a hematological malignancy. Also disclosed herein are compositions and methods for the treatment of Ewing's Sarcoma. Said compositions comprise isoform selective pyrrolo-pyrazole PKC inhibitors.

What is claimed is: 
     
         1 . A method of treating a hematological malignancy in an individual in need thereof, comprising administering to the individual a pharmaceutical composition comprising 5-{[(2S,5R)-2,5-dimethyl-4-(tetrahydro-2H-pyran-4-ylmethyl)piperazin-1-yl]carbonyl}-N-(5-fluoro-2-methylpyrimidin-4-yl)-6,6-dimethyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-amine, or a pharmaceutically acceptable salt thereof, wherein the hematological malignancy is small lymphocytic leukemia. 
     
     
         2 . The method of  claim 1 , wherein the small lymphocytic leukemia is relapsed or refractory small lymphocytic leukemia. 
     
     
         3 . The method of  claim 1 , wherein use of ibrutinib in the treatment of said hematological malignancy is unsuitable or otherwise contraindicated. 
     
     
         4 . The method of  claim 2 , wherein use of ibrutinib in the treatment of said hematological malignancy is unsuitable or otherwise contraindicated. 
     
     
         5 . The method of  claim 2 , wherein the relapsed or refractory small lymphocytic leukemia is refractory to a BTK inhibitor. 
     
     
         6 . The method of  claim 5 , wherein the BTK inhibitor is ibrutinib. 
     
     
         7 . The method of  claim 5 , wherein the BTK inhibitor is acalabrutinib. 
     
     
         8 . The method of  claim 2 , wherein the relapsed or refractory small lymphocytic leukemia is relapsed after treatment with a BTK inhibitor. 
     
     
         9 . The method of  claim 8 , wherein the BTK inhibitor is ibrutinib. 
     
     
         10 . The method of  claim 8 , wherein the BTK inhibitor is acalabrutinib. 
     
     
         11 . A method of treating a small lymphocytic leukemia in an individual in need thereof, comprising administering to the individual: (a) a composition comprising 5-{[(2S,5R)-2,5-Dimethyl-4-(tetrahydro-2H-pyran-4-ylmethyl)piperazin-1-yl]carbonyl}-N-(5-fluoro-2-methylpyrimidin-4-yl)-6,6-dimethyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-amine, or a pharmaceutically acceptable salt thereof; and (b) a BTK inhibitor. 
     
     
         12 . The method of  claim 9 , wherein the BTK inhibitor is ibrutinib. 
     
     
         13 . The method of  claim 9 , wherein the BTK inhibitor is acalabrutinib. 
     
     
         14 . The method of  claim 9 , wherein the BTK inhibitor is selected from the group consisting of GS-4059, spebrutinib, BGB-3111, M7583, MSC2364447C, BIIB068, AC0058TA, and DTRMWXHS-12. 
     
     
         15 . The method of  claim 1 , wherein the method is characterized by the occurrence of lymphocytosis. 
     
     
         16 . The method of  claim 2 , wherein the method is characterized by the occurrence of lymphocytosis. 
     
     
         17 . The method of  claim 5 , wherein the method is characterized by the occurrence of lymphocytosis. 
     
     
         18 . The method of  claim 8 , wherein the method is characterized by the occurrence of lymphocytosis.