# US 10,226,478 B2 · Dosage regimen for sapacitabine and decitabine in combination for treating acute myeloid leukemia > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,226,478 B2 - Document ID: US10226478B2 - Status: Granted - Kind: B2 - Application number: 14/111,430 - Filed: 2012-04-13 - Published: 2014-04-03 - Granted: 2019-03-12 - Earliest claimed: 2011-04-14 - Assignees: Cyclacel Limited - Applicants: Judy H. Chiao - Inventors: Judy H. Chiao - Web page: https://patentgrep.com/patent/US10226478B2 ## CPC - A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid - A61K 31/706: containing six-membered rings with nitrogen as a ring hetero atom - A61P 35/02: specific for leukemia - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## 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 ### Claim 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. ### Claim 2 (depends on 1) A method according to claim 1 wherein the second treatment cycle comprises administering a therapeutically effective amount of sapacitabine. ### Claim 3 (depends on 1) A method according to claim 1 wherein the metabolite of sapacitabine is 1-(2-C-Cyano-2-deoxy-β-D-arabino-pentafuranosyl)-cytosine (CNDAC). ### Claim 4 (depends on 1) 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. ### Claim 5 (depends on 1) 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. ### Claim 6 (depends on 1) A method according to claim 1, which comprises two or more of each treatment cycle. ### Claim 7 (depends on 6) A method according to claim 6, which comprises two to four of each treatment cycle. ### Claim 8 (depends on 1) A method according to claim 1, wherein the decitabine is administered intravenously. ### Claim 9 (depends on 1) A method according to claim 1, which comprises three or more of each treatment cycle. ### Claim 10 (depends on 1) A method according to claim 1, which comprises four or more of each treatment cycle. ### Claim 11 (depends on 1) A method according to claim 1, which comprises five or more of each treatment cycle. ### Claim 12 (depends on 1) A method according to claim 1, wherein the decitabine is administered in a dose of from about 10 to about 20 mg/m2. ### Claim 13 (depends on 12) A method according to claim 12, wherein the decitabine is administered in a dose of about 20 mg/m2 per day. ### Claim 14 (depends on 1) A method according to claim 1, wherein the sapacitabine or metabolite thereof is administered orally. ### Claim 15 (depends on 14) 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. ### Claim 16 (depends on 14) A method according to claim 14, wherein the sapacitabine or metabolite thereof is administered in a dose of about 300 mg b.i.d. ### Claim 17 (depends on 1) A method according to claim 1, wherein the patient is 75 years of age or over. ### Claim 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. ### Claim 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. ### Claim 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. ### Claim 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.