Methods for Treating Hematopoietic Neoplasms

Abstract

This invention relates to methods for treating, preventing and/or managing hematopoietic neoplasm in a subject by administering to the subject combretastatin A-4 phosphate, or a pharmaceutically acceptable salt thereof. The method may further comprise co-administering a chemotherapeutic agent.

1 . A method of treating a hematopoietic neoplasm comprising administering a therapeutically effective amount of combretastatin A-4 phosphate (CA4P), or a pharmaceutically acceptable salt thereof, to a subject having a hematological malignancy. 
   
   
       2 . The method of  claim 1 , wherein the combretastatin A-4 phosphate salt is a compound of the Formula II: 
     
       
         
         
             
             
         
       
       wherein 
       each OR 1  and OR 2  independently is selected from OH, —O − QH +  and —O − M + , wherein M +  is a monovalent or divalent metal cation, and Q is: 
       a) an amino acid containing at least two nitrogen atoms where one of the nitrogen atoms, together with a proton, forms a quaternary ammonium cation QH + ; or 
       b) an organic amine containing at least one nitrogen atom which, together with a proton, forms a quaternary ammonium cation, QH + . 
     
   
   
       3 . The method of  claim 2 , wherein one of OR 1  and OR 2  is hydroxyl and the other is —O − QH +  and Q is tromethamine or L-histidine. 
   
   
       4 . The method of  claim 1 , wherein the combretastatin A-4 phosphate salt is a compound of the Formula II: 
     
       
         
         
             
             
         
       
       wherein 
     
     each OR 1  and OR 2  independently is selected from OH, and —O − M + , wherein each M +  independently is an aliphatic organic amine, an alkali metal, a transition metal, a heteroarylene, a heterocyclyl, a nucleoside, a nucleotide, an alkaloid, an amino sugar, an amino nitrile, or an nitrogenous antibiotic. 
   
   
       5 . The method of  claim 4 , wherein each M + , independently, is selected from the group consisting of sodium, TRIS, histidine, ethanolamine, diethanolamine, ethylenediamine, diethylamine, triethanolamine, glucamine, N-methylglucamine, ethylenediamine, 2-(4-imidazolyl)-ethylamine, choline, and hydrabamine. 
   
   
       6 . The method of  claim 1 , wherein the hematopoietic neoplasm is a myeloid neoplasm. 
   
   
       7 . The method of  claim 6 , wherein the hematopoietic neoplasm is an acute myeloid leukemia (AML). 
   
   
       8 . The method of  claim 1 , wherein the hematopoietic neoplasm is a lymphoid neoplasm. 
   
   
       9 . The method of  claim 1 , wherein the hematopoietic neoplasm is a refractory organ-infiltrating leukemia. 
   
   
       10 . The method of  claim 1 , wherein the pharmaceutically acceptable salt is a tromethamine salt of combretastatin A-4 phosphate. 
   
   
       11 . The method of  claim 1 , further comprising co-administering a chemotherapeutic agent to the subject having a hematological malignancy. 
   
   
       12 . The method of  claim 11 , wherein the chemotherapeutic agent is Ara-C, etoposide, thioguanine or cyclophosphamide.