Formulations of bendamustine

Abstract

Methods of treatment using bendamustine formulations designed for small volume intravenous administration are disclosed. The methods conveniently allow shorter administration time without the active ingredient coming out of solution as compared to presently available formulations.

We claim: 
     
         1 . A method of treating cancer or malignant disease in a subject, comprising parenterally administering to a subject in need thereof, a volume of about 100 ml or less of a liquid composition comprising:
 from about 0.05 to about 6 mg/ml of bendamustine or a pharmaceutically acceptable salt thereof;   a parenterally acceptable diluent; and   optionally an antioxidant;   
       over a substantially continuous period of less than or equal to about 30 minutes. 
     
     
         2 . The method of  claim 1 , wherein the liquid composition comprises from about 0.05 to about 3.2 mg/ml of bendamustine or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The method of  claim 1 , wherein the total impurities in the liquid composition are less than about 5%, as determined by HPLC at a wavelength of 223 nm after the liquid composition is stored for 15 months at a temperature of from about 5° C. to about 25° C. 
     
     
         4 . The method of  claim 1 , wherein the liquid composition is administered over a period of about 15 minutes. 
     
     
         5 . The method of  claim 1 , wherein the liquid composition is administered over a period of about 10 minutes. 
     
     
         6 . The method of  claim 1 , wherein the subject is being treated for chronic lymphocytic leukemia. 
     
     
         7 . The method of  claim 6 , wherein the diluted composition is administered in about 10 minutes. 
     
     
         8 . The method of  claim 7 , wherein the liquid composition is administered intravenously in a volume of about 50 mL in about 10 minutes or less on days 1 and 2 of a 28 day cycle. 
     
     
         9 . The method of  claim 8 , wherein the method is repeated for up to 6 cycles. 
     
     
         10 . The method of  claim 7 , wherein the subject is administered a bendamustine dosage amount ranging from about 25 mg/m 2  to about 100 mg/m 2 . 
     
     
         11 . The method of  claim 10 , wherein the bendamustine dosage amount is about 100 mg/m 2 . 
     
     
         12 . The method of  claim 1 , wherein the bendamustine is administered to treat indolent B cell non-Hodgkin's lymphoma. 
     
     
         13 . The method of  claim 12 , wherein the diluted composition is administered in about 10 minutes. 
     
     
         14 . The method of  claim 12 , wherein the liquid composition is administered intravenously in a volume of about 50 mL in about 10 minutes or less on days 1 and 2 of a 21 day cycle. 
     
     
         15 . The method of  claim 14 , wherein the method is repeated for up to 8 cycles. 
     
     
         16 . The method of  claim 12 , wherein the subject is administered a bendamustine dosage amount ranging from about 60 mg/m 2  to about 120 mg/m 2 . 
     
     
         17 . The method of  claim 16 , wherein the subject is administered a bendamustine dosage amount of about 120 mg/m 2 . 
     
     
         18 . The method of  claim 16 , wherein the bendamustine dosage amount is about 100 mg/m 2 . 
     
     
         19 . The method of  claim 1 , wherein the parenterally acceptable diluent comprises Water for Injection, 0.9% saline, 0.45% saline, or 2.5% dextrose/0.45% saline.