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

• US 10,226,478 B2
• Filed: 04/13/2012
• Issued: 03/12/2019
• Est. Priority Date: 04/14/2011
• Status: Active Grant

• Current Assignee: Cyclacel Pharmaceuticals Incorporated
• Original Assignee: Cyclacel Pharmaceuticals Incorporated
• Inventors: Chiao, Judy H.
• Primary Examiner(s): Lau, Jonathan S
• Application Number:
  US14/111,430
• Publication Number:
  US 20140094428A1
• Time in Patent Office: 2,524 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. A method of treating acute myeloid leukemia (AML) in a subject of 70 years of age or over, said method comprising administering to the 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 followed by at least one second treatment cycle,

wherein said first treatment cycle comprises administering a therapeutically effective amount of decitabine for 5 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, in a dose of about 100-400 mg b.i.d. 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.

2. A method according to claim 1 wherein the second treatment cycle comprises administering a therapeutically effective amount of sapacitabine.

3. A method according to claim 1 wherein the metabolite of sapacitabine is 1-(2-C-Cyano-2-deoxy-β

-D-arabino-pentafuranosyl)-cytosine (CNDAC).

4. A method according to claim 1, wherein said first treatment cycle comprises administering a therapeutically effective amount of decitabine for 5 days followed by a 3 week rest period.

5. A method according to claim 1, wherein said second treatment cycle comprises administering a therapeutically effective amount of sapacitabine or metabolite thereof for 3 consecutive days per week, for 2 weeks followed by a 2 week rest period.

6. A method according to claim 1, which comprises two or more of each treatment cycle.

7. A method according to claim 6, which comprises two to four of each treatment cycle.

8. A method according to claim 1, wherein the decitabine is administered intravenously.

9. A method according to claim 1, which comprises three or more of each treatment cycle.

10. A method according to claim 1, which comprises four or more of each treatment cycle.

11. A method according to claim 1, which comprises five or more of each treatment cycle.

12. A method according to claim 1, wherein the decitabine is administered in a dose of from about 10 to about 20 mg/m².

13. A method according to claim 12, wherein the decitabine is administered in a dose of about 20 mg/m² per day.

14. A method according to claim 1, wherein the sapacitabine or metabolite thereof is administered orally.

15. A method according to claim 14, wherein the sapacitabine or metabolite thereof is administered in a dose of about 250-300 mg b.i.d.

16. A method according to claim 14, wherein the sapacitabine or metabolite thereof is administered in a dose of about 300 mg b.i.d.

17. A method according to claim 1, wherein the patient is 75 years of age or over.

18. A method of treating acute myeloid leukemia (AML) in a subject of 70 years of age or over, said method comprising administering to the subject a therapeutically effective amount of (i) sapacitabine;

and (ii) decitabine;

in accordance with a dosing regimen comprising at least one first treatment cycle followed by at least one second treatment cycle,

wherein said first treatment cycle comprises administering decitabine intravenously in a dose of about 20 mg/m² per day for 5 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.

19. A method of treating acute myeloid leukemia (AML) in a subject of 75 years of age or over, said method comprising administering to the subject a therapeutically effective amount of (i) sapacitabine;

and (ii) decitabine;

in accordance with a dosing regimen comprising at least one first treatment cycle followed by at least one second treatment cycle,

wherein said first treatment cycle comprises administering decitabine intravenously in a dose of about 20 mg/m² per day for 5 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.

20. A method of treating acute myeloid leukemia (AML) in a subject of 75 years of age or over, said method comprising administering to the 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 followed by at least one second treatment cycle,

wherein said first treatment cycle comprises administering a therapeutically effective amount of decitabine for 5 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, in a dose of about 100-400 mg b.i.d. for 3consecutive 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.

21. A method of treating acute myeloid leukemia (AML) in a subject of 70 years of age or over, said method comprising administering to the 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 followed by at least one second treatment cycle,

wherein said first treatment cycle comprises administering a therapeutically effective amount of decitabine for 5 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, in a dose of about 100-400 mg b.i.d. for 3consecutive 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;

and wherein said dosing regimen comprises two or more of each treatment cycle.