DOSAGE REGIMEN FOR SAPACITABINE AND DECITABINE IN COMBINATION FOR TREATING ACUTE MYELOID LEUKEMIA

• US 20190314396A1
• Filed: 01/16/2019
• Published: 10/17/2019
• Est. Priority Date: 04/14/2011
• Status: Abandoned Application

• Current Assignee: Cyclacel Pharmaceuticals Incorporated
• Original Assignee: Cyclacel Pharmaceuticals Incorporated
• Inventors: CHIAO, Judy H.
• Application Number:
  US16/249,274
• Publication Number:
  US 20190314396A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/706 containing six-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61P 35/02 specific for 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.

Claims

1-24. -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.

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/m² 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/m² 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/m² per day for 5 days.

32. The kit of parts according to claim 28, wherein the decitabine is formulated for administration of 20 mg/m² 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.

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/m² 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.

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.

27. (canceled)