Use of c-src inhibitors alone or in combination with sti571 for the treatment of leukaemia

Abstract

The invention relates to a combination which comprises (a) at least one compound decreasing the c-Src activity and (b) N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamdio]-2-methylphenyl }-4-(3-pyridyl)-2-pyrimidine-amine or the monomethanesulfonate salt thereof; to pharmaceutical compositions comprising said combinations; and to a method of treating a warm-blooded animal having leukaemia, especially chronic myelogenous leukaemia, comprising administering to the animal at least one compound inhibiting the activity of a member of the Src kinase family, the Tec kinase family or a Raf kinase inhibitor, in particular inhibiting the c-Src protein tyrosine kinase activity or inhibiting simultaneously the c-Src protein tyrosine kinase activity and the Bcr-Abl tyrosine kinase activity, alone or in combination with a Bcr-Abl inhibitor, in particular N- {5- [4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl }-4-(3-pyridyl)-2-pyrimidine-amine.

1 - 19 . (canceled)  
     
     
         20 . A combination which comprises (a) a compound of formula I  
       
         
           
           
               
               
           
         
       
       and (b) N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine, wherein each compound is present in free form or in the form of a pharmaceutically acceptable salt, and optionally at least one pharmaceutically acceptable carrier; for simultaneous, or sequential use.  
     
     
         21 . The combination according to  claim 20  wherein compound (b) is used in the form of its monomethanesulfonate salt.  
     
     
         22 . A method of treating leukaemia in a warm-blooded animal comprising administering to said animal an effective amount of N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine in combination with an effective amount of a compound of formula I  
       
         
           
           
               
               
           
         
       
       wherein the active ingredients are present in free form or in the form of a pharmaceutically acceptable salt.  
     
     
         23 . The method according to  claim 22  wherein said leukaemia is resistant to mono-therapy employing N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine as sole active agent.  
     
     
         24 . The method according to  claim 22  wherein said leukaemia is chronic myelogenous leukaemia.  
     
     
         25 . A pharmaceutical composition comprising the combination according to  claim 20  and at least one pharmaceutically acceptable carrier.