Cerdulatinib for the treatment of b-cell malignancies

Abstract

Provided herein are compositions and methods for treating a relapsed or refractory hematologic cancer in a human patient in need thereof. The methods entail administering to the patient a daily dose of about 10 mg to about 75 mg of cerdulatinib or a pharmaceutically acceptable salt thereof, wherein the patients suffer one or more of a B-cell malignancy, chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) or other transformed FL and/or have relapsed or not responded to a prior chemotherapy.

1 . A method of treating a hematologic cancer in a human patient in need thereof, comprising administering to the patient a daily dose of about 10 mg to about 75 mg of cerdulatinib or a pharmaceutically acceptable salt thereof. 
     
     
         2 . A method for treating a relapsed or refractory hematologic cancer in a patient in need thereof, comprising administering to the patient an effective amount of cerdulatinib, or a pharmaceutically acceptable salt thereof. 
     
     
         3 . A method for treating a relapsed or refractory hematologic cancer in a patient in need thereof, comprising administering to the patient an effective amount of cerdulatinib, or a pharmaceutically acceptable salt thereof, wherein:
 the patient has a mutation linked to relapse and/or a resistance to a drug for treating a hematological cancer; and   the effective amount is cerdulatinib, or a pharmaceutically acceptable salt thereof, is a daily dose of about 30 mg to about 80 mg of cerdulatinib.   
     
     
         4 . The method of  claim 1  or  2 , wherein the patient has a mutation linked to relapse and/or a resistance to a drug for treating a hematological cancer. 
     
     
         5 . The method of  claim 3  or  4 , wherein the patient has a del17p mutation, a P53 mutation, an ATM mutation, a STAT mutation, a STAT 6 mutation, a C481S STAT6 mutation, a mutation associated with the NOTCH pathway, or a mutation associated with the Caderin pathway. 
     
     
         6 . The method of any of  claims 3 - 5 , wherein the patient does not have a mutation in all of P53, BTK, and EP300. 
     
     
         7 . The method of  claim 3  or  4 , wherein the patient has a BTK mutation. 
     
     
         8 . The method of  claim 3  or  4 , wherein the patient has a resistance to ibrutinib. 
     
     
         9 . The method of any one of the preceding claims, wherein the hematologic cancer is selected from the group consisting of non-Hodgkin's lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Follicular Lymphoma (FL), transformed Follicular Lymphoma (tFL), Diffuse Large B-cell Lymphoma (DLBCL), and Mantle Cell Lymphoma (MCL). 
     
     
         10 . The method of  claim 9 , wherein the hematologic cancer is CLL. 
     
     
         11 . The method of  claim 9 , wherein the hematologic cancer is SLL. 
     
     
         12 . The method of  claim 9 , wherein the hematologic cancer is FL. 
     
     
         13 . The method of  claim 9 , wherein the hematologic cancer is tFL. 
     
     
         14 . The method of  claim 9 , wherein the hematologic cancer is DLBCL. 
     
     
         15 . The method of  claim 9 , wherein the hematologic cancer is MCL. 
     
     
         16 . The method of any one of the preceding claims, wherein the patient was previously administered a drug selected from the group consisting of an alkylating agent, an anti-CD20 antibody, a BCL-2 inhibitor, a BTK inhibitor, a PI3Kδ inhibitor, a platinum-based drug, an antimetabolite, an anthracycline, a BCR pathway inhibitor, and another chemotherapeutic agent used for treating a hematologic cancer. 
     
     
         17 . The method of  claims 1 - 16 , wherein the patient was previously administered a drug selected from the group consisting of venetoclax, rituximab, ibrutinib, idelalisib, and fludararbine. 
     
     
         18 . The method of any of the preceding claims, wherein the cerdulatinib is administered in a pharmaceutical composition further comprising a pharmaceutically acceptable excipient or carrier. 
     
     
         19 . The method of  claim 1 , wherein the daily dose of cerdulatinib is about 70 mg. 
     
     
         20 . The method of  claim 1 , wherein the daily dose of cerdulatinib is administered twice daily at about 35 mg per dose. 
     
     
         21 . The method of  claim 2  or  3 , wherein the effective amount of cerdulatinib, or a pharmaceutically acceptable salt thereof, is administered at doses of about 15 mg to about 40 mg twice daily. 
     
     
         22 . The method of  claim 2  or  3 , wherein the effective amount of cerdulatinib, or a pharmaceutically acceptable salt thereof, is administered at doses of about 30 mg to about 40 mg twice daily. 
     
     
         23 . The method of  claim 2  or  3 , wherein the effective amount of cerdulatinib, or a pharmaceutically acceptable salt thereof, is administered at doses of about 35 mg twice daily.