Dosage regimen for sapacitabine and decitabine in combination for treating acute myeloid leukemia

Abstract

A first aspect of the invention relates to a method of treating AML in a subject, said method comprising administering to a subject a therapeutically effective amount of (i) sapacitabine, or a metabolite thereof; and (ii) decitabine; in accordance with a dosing regimen comprising at least one first treatment cycle and at least one second treatment cycle, wherein said first treatment cycle comprises administering a therapeutically effective amount of decitabine for 5 to 10 consecutive days followed by a rest period of from 3 to 5 weeks, or until treatment-related toxicities are resolved, whichever is longer; and wherein said second treatment cycle comprises administering a therapeutically effective amount of sapacitabine, or a metabolite thereof, for 3 consecutive days per week, for 2 weeks followed by a rest period of from 2 to 4 weeks, or until treatment-related toxicities are resolved, whichever is longer.

1 - 24 . (canceled) 
     
     
         25 . A kit of parts comprising:
 (i) sapacitabine, or a metabolite thereof;   (ii) decitabine; and   (iii) instructions for administering sapacitabine, or a metabolite thereof, and decitabine in accordance with a dosing regimen comprising at least one first treatment cycle and at least one second treatment cycle,
 wherein said first treatment cycle comprises administering a therapeutically effective amount of decitabine for 5 to 10 consecutive days followed by a rest period of from 3 to 5 weeks, or until treatment-related toxicities are resolved, whichever is longer; and 
 wherein said second treatment cycle comprises administering a therapeutically effective amount of sapacitabine, or a metabolite thereof, for 3 consecutive days per week, for 2 weeks followed by a rest period of from 2 to 4 weeks, or until treatment-related toxicities are resolved, whichever is longer. 
   
     
     
         26 . A kit of parts comprising:
 (i) sapacitabine, or a metabolite thereof;   (ii) decitabine; and   (iii) instructions for administering sapacitabine, or a metabolite thereof, and decitabine in accordance with a dosing regimen comprising at least one first treatment cycle and at least one second treatment cycle,
 wherein said first treatment cycle comprises administering decitabine intravenously in a dose of about 20 mg/m 2  for 5 to 10 consecutive days followed by a 3 to 5 week rest period, or until treatment-related toxicities are resolved, whichever is longer; and 
 wherein said second treatment cycle comprises administering sapacitabine orally in a dose of about 300 mg b.i.d. for 3 consecutive days per week, for 2 weeks followed by a 2 to 4 week rest period, or until treatment-related toxicities are resolved, whichever is longer. 
   
     
     
         27 . (canceled) 
     
     
         28 . The kit of parts according to  claim 25 , wherein the decitabine is formulated for intravenous administration. 
     
     
         29 . The kit of parts according to  claim 28 , wherein the decitabine is formulated for administration of 10 to 20 mg/m 2  per day for 5 to 10 days. 
     
     
         30 . The kit of parts according to  claim 29 , wherein the decitabine is formulated for administration of 15 mg/m 2  per day for 5 to 10 days. 
     
     
         31 . The kit of parts according to  claim 29 , wherein the decitabine is formulated for administration of 20 mg/m 2  per day for 5 days. 
     
     
         32 . The kit of parts according to  claim 28 , wherein the decitabine is formulated for administration of 20 mg/m 2  per day for 10 days. 
     
     
         33 . The kit of parts according to  claim 28 , wherein the decitabine is formulated in unit dosage form. 
     
     
         34 . The kit of parts according to  claim 25 , wherein the sapacitabine, or metabolite thereof, is formulated for oral administration. 
     
     
         35 . The kit of parts according to  claim 34 , wherein the sapacitabine, or metabolite thereof, is administered as a single dose per day. 
     
     
         36 . The kit of parts according to  claim 34 , wherein the sapacitabine, or metabolite thereof, is divided into separate dosages for administration two, three or four times per day. 
     
     
         37 . The kit of parts according to  claim 34 , wherein the sapacitabine, or metabolite thereof, is administered twice per day (b.i.d.). 
     
     
         38 . The kit of parts according to  claim 34 , wherein the sapacitabine, or metabolite thereof, is formulated for oral administration of 100-800 mg per day. 
     
     
         39 . The kit of parts according to  claim 35 , wherein the sapacitabine, or metabolite thereof, is formulated for oral administration of 100-400 mg per day. 
     
     
         40 . The kit of parts according to  claim 35 , wherein the sapacitabine, or metabolite thereof, is formulated for oral administration of 250-300 mg per day. 
     
     
         41 . The kit of parts according to  claim 35 , wherein the sapacitabine, or metabolite thereof, is formulated for oral administration of 300 mg per day. 
     
     
         42 . The kit of parts according to  claim 34 , wherein the sapacitabine, or metabolite thereof, is in unit dosage form. 
     
     
         43 . The kit of parts according to  claim 42 , wherein the unit dosage form of the sapacitabine, or metabolite thereof, is a pill, tablet, gellule, drop or capsule. 
     
     
         44 . The kit of parts according to  claim 25 , wherein the metabolite of sapacitabine is 1-(2-C-Cyano-2-deoxy-β-D-arabino-pentafuranosyl)-cytosine (CNDAC). 
     
     
         45 . The kit of parts according to  claim 25 , wherein each of (i) the sapacitabine or metabolite thereof, and (ii) the decitabine, are present in an amount sufficient for two or more of each treatment cycle. 
     
     
         46 . The kit of parts according to  claim 25 , wherein each of (i) the sapacitabine or a metabolite thereof, and (ii) the decitabine, are present in an amount sufficient for two to four of each treatment cycle. 
     
     
         47 . The kit of parts according to  claim 25 , for use in treating acute myeloid leukemia (AML) in a subject. 
     
     
         48 . The kit of parts according to  claim 47 , wherein the subject is 70 years of age or over. 
     
     
         49 . The kit of parts according to  claim 26 , wherein the decitabine is formulated in unit dosage form. 
     
     
         50 . The kit of parts according to  claim 26 , wherein the sapacitabine or metabolite thereof is formulated in unit dosage form. 
     
     
         51 . The kit of parts according to  claim 26 , wherein the metabolite of sapacitabine is 1-(2-C-Cyano-2-deoxy-β-D-arabino-pentafuranosyl)-cytosine (CNDAC). 
     
     
         52 . The kit of parts according to  claim 26 , wherein each of (i) the sapacitabine or metabolite thereof, and (ii) the decitabine, are present in an amount sufficient for two or more of each treatment cycle. 
     
     
         53 . The kit of parts according to  claim 26 , wherein each of (i) the sapacitabine or a metabolite thereof, and (ii) the decitabine, are present in an amount sufficient for two to four of each treatment cycle. 
     
     
         54 . The kit of parts according to  claim 26 , for use in treating acute myeloid leukemia (AML) in a subject. 
     
     
         55 . The kit of parts according to  claim 26 , wherein the subject is 70 years of age or over.