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 chronic lymphocytic leukemia 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. 
     
     
         2 . The method of  claim 1 , wherein use of ibritinub is unsuitable or otherwise contraindicated. 
     
     
         3 . A method of treating a chronic 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. 
     
     
         4 . The method of  claim 3 , wherein the BTK inhibitor is ibrutinib. 
     
     
         5 . The method of  claim 3 , wherein the BTK inhibitor is acalabrutinib. 
     
     
         6 . The method of  claim 3 , wherein the BTK inhibitor is selected from the group consisting of GS-4059, spebrutinib, BGB-3111, M7583, MSC2364447C, BIIB068, AC0058TA, and DTRMWXHS-12. 
     
     
         7 . The method of  claim 1 , wherein the method is characterized by the occurrence of lymphocytosis.