Therapies for hematologic malignancies

Abstract

The invention provides methods that relate to a novel therapeutic strategy for the treatment of hematological malignancies and inflammatory diseases. In particular, the method comprises administration of a compound of formula A, wherein R is H, halo, or C1-C6 alkyl; R′ is C1-C6 alkyl; or a pharmaceutically acceptable salt thereof; and optionally a pharmaceutically acceptable excipient.

1 . A method of treating a solid tumor in a human comprising administering to said human a compound of formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The method of  claim 1 , wherein the solid tumor is selected from the group consisting of pancreatic cancer, bladder cancer, colorectal cancer, breast cancer, prostate cancer, renal cancer, hepatocellular cancer, lung cancer, ovarian cancer, cervical cancer, gastric cancer, esophageal cancer, head and neck cancer, melanoma, neuroendocrine cancers, brain tumors, bone cancer, and soft tissue sarcoma. 
     
     
         3 . The method of  claim 2 , wherein the solid tumor is selected pancreatic cancer. 
     
     
         4 . The method of  claim 1 , wherein the human is refractory to chemotherapy treatment, or in relapse after treatment with chemotherapy. 
     
     
         5 . The method of  claim 1 , wherein the compound of formula I or pharmaceutically acceptable salt thereof is administered at a dose of 20-500 mg/day. 
     
     
         6 . The method of  claim 1 , wherein the compound of formula I or pharmaceutically acceptable salt thereof is administered at a dose of 50-250 mg/day. 
     
     
         7 . The method of  claim 1 , wherein the compound of formula I or pharmaceutically acceptable salt thereof is administered at a dose of 50-150 mg twice per day. 
     
     
         8 . The method of  claim 1 , wherein the compound of formula I or pharmaceutically acceptable salt thereof is administered at least twice daily. 
     
     
         9 . The method of  claim 1 , wherein the compound of formula I or pharmaceutically acceptable salt thereof maintains an average blood plasma concentration between 100 nM and 1100 nM over a period of at least 12 hours from compound administration. 
     
     
         10 . The method of  claim 1 , further comprising administering at least one additional agent to the human. 
     
     
         11 . The method of  claim 10 , wherein the at least one additional agent is selected from the group consisting of rituximab, ofatumumab, Bortezomib (Velcade®), Carfilzomib (PR-171), PR-047, disulfuram, lactacystin, PS-519, eponemycin, epoxomycin, aclacinomycin, CEP-1612, MG-132, CVT-63417, PS-341, vinyl sulfone tripeptide inhibitors, ritonavir, PI-083, (+/−)-7-methylomuralide, and (−)-7-methylomuralide.