# US 10,245,258 B2 · Treatment of a hematologic malignancy with 2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,245,258 B2 - Document ID: US10245258B2 - Status: Granted - Kind: B2 - Application number: 15/614,434 - Filed: 2017-06-05 - Published: 2017-12-07 - Granted: 2019-04-02 - Earliest claimed: 2016-06-06 - Assignees: Celgene Corporation - Applicants: Celgene Corporation - Inventors: Soraya Carrancio; Paul Hollenbach; Antonia Lopez-Girona; Kyle MacBeth; Michael Pourdehnad; Irit Rappley; Gang Lu - Web page: https://patentgrep.com/patent/US10245258B2 ## CPC - A61K 31/454: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} - 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 Provided herein are methods of treating, preventing, managing, and/or ameliorating leukemia or myelodysplastic syndrome comprising administering 2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide or a stereoisomer or mixture of stereoisomers, an isotopologue, pharmaceutically acceptable salt, tautomer, solvate, hydrate, co-crystal, clathrate, or polymorph thereof to a patient. ## Claims ### Claim 1 A method for treating, managing, or ameliorating a hematological cancer comprising administering to a subject in need thereof 2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide, which has the following structure: or a stereoisomer or mixture of stereoisomers, isotopologue, pharmaceutically acceptable salt, tautomer, solvate, hydrate, co-crystal, clathrate, or polymorph thereof (Compound 1), wherein Compound 1 is administered to the subject in a dose of about 0.1 mg to about 20 mg, and the subject is further administered one or more of calcium, calcitriol, or vitamin D supplementation. ### Claim 2 (depends on 1) The method of claim 1, wherein the hematological cancer is acute myeloid leukemia. ### Claim 3 (depends on 2) The method of claim 2, wherein the acute myeloid leukemia is refractory or relapsed acute myeloid leukemia. ### Claim 4 (depends on 1) The method of claim 1, wherein Compound 1 is administered on days 1 to 5 of a 28 day treatment cycle. ### Claim 5 (depends on 4) The method of claim 4, wherein the treatment cycle comprises a rest period of 23 days. ### Claim 6 (depends on 1) The method of claim 1, wherein Compound 1 is administered on days 1 to 5 of a 42 day treatment cycle. ### Claim 7 (depends on 1) The method of claim 1, wherein Compound 1 is administered on days 1 to 3 of a 28 day treatment cycle. ### Claim 8 (depends on 1) The method of claim 1, wherein Compound 1 is administered on days 1 to 5 and days 15 to 19 of a 28 day treatment cycle. ### Claim 9 (depends on 4) The method of claim 4, wherein the treatment cycle is repeated at least once. ### Claim 10 (depends on 4) The method of claim 4, wherein the treatment cycle is repeated 2 to 4 times. ### Claim 11 (depends on 1) The method of claim 1, wherein Compound 1 is administered in a dose of about 0.1 mg to about 10 mg. ### Claim 12 (depends on 1) The method of claim 1, wherein Compound 1 is administered in a dose from about 0.3 mg to about 8.1 mg. ### Claim 13 (depends on 1) The method of claim 1, wherein Compound 1 is administered in a dose of about 0.3 mg, 0.6 mg, 1.2 mg, 2.4 mg, 3.6 mg, 5.4 mg or 8.1 mg. ### Claim 14 (depends on 1) The method of claim 1, wherein Compound 1 is administered in a dose of about 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3.6 mg. ### Claim 15 (depends on 1) The method of claim 1, wherein the subject is administered one or more of calcium, calcitriol, or vitamin D supplementation prior to administration of Compound 1. ### Claim 16 (depends on 1) The method of claim 1, wherein the subject is administered one or more of calcium, calcitriol, or vitamin D supplementation at least 3 days prior to administration of Compound 1 on day 1 of the cycle. ### Claim 17 (depends on 1) The method of claim 1, wherein the subject does not have a disorder disrupting normal calcium homeostasis or preventing calcium supplementation. ### Claim 18 (depends on 1) The method of claim 1 comprising administering a polymorph of (2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide). ### Claim 19 (depends on 1) The method of claim 1 comprising administering an amorphous form of (2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide). ### Claim 20 (depends on 1) The method of claim 1 comprising administering a lyophilized formulation of Compound 1, wherein the lyophilized formulation comprises Compound 1, a buffer and a bulking agent. ### Claim 21 (depends on 1) The method of claim 1, further comprising administering a therapeutically effective amount of a second active agent or a supportive care therapy. ### Claim 22 (depends on 1) The method of claim 1, wherein the subject is a patient 18 years or older. ### Claim 23 (depends on 1) The method of claim 1, wherein the hematological cancer is myelodysplastic syndrome. ### Claim 24 (depends on 23) The method of claim 23, wherein the myelodysplastic syndrome is refractory or relapsed myelodysplastic syndrome. ### Claim 25 (depends on 23) The method of claim 23, wherein Compound 1 is administered on days 1 to 5 of a 28 day treatment cycle. ### Claim 26 (depends on 23) The method of claim 23, wherein Compound 1 is administered on days 1 to 5 of a 42 day treatment cycle. ### Claim 27 (depends on 23) The method of claim 23, wherein Compound 1 is administered on days 1 to 3 of a 28 day treatment cycle. ### Claim 28 (depends on 23) The method of claim 23, wherein Compound 1 is administered on days 1 to 5 and days 15 to 19 of a 28 day treatment cycle. ### Claim 29 (depends on 25) The method of claim 25, wherein the treatment cycle is repeated at least once. ### Claim 30 (depends on 25) The method of claim 25, wherein the treatment cycle is repeated 2 to 4 times. ### Claim 31 (depends on 23) The method of claim 23, wherein Compound 1 is administered in a dose of about 0.1 mg to about 10 mg. ### Claim 32 (depends on 23) The method of claim 23, wherein Compound 1 is administered in a dose from about 0.3 mg to about 8.1 mg. ### Claim 33 (depends on 23) The method of claim 23, wherein Compound 1 is administered in a dose of about 0.3 mg, 0.6 mg, 1.2 mg, 2.4 mg, 3.6 mg, 5.4 mg or 8.1 mg. ### Claim 34 (depends on 23) The method of claim 23, wherein Compound 1 is administered in a dose of about 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3.6 mg. ### Claim 35 (depends on 23) The method of claim 23, wherein the subject is administered one or more of calcium, calcitriol, or vitamin D supplementation. ### Claim 36 (depends on 35) The method of claim 35, wherein the subject is administered one or more of calcium, calcitriol, or vitamin D supplementation prior to administration of Compound 1. ### Claim 37 (depends on 35) The method of claim 35, wherein the subject is administered one or more of calcium, calcitriol, or vitamin D supplementation at least 3 days prior to administration of Compound 1 on day 1 of the cycle. ### Claim 38 (depends on 23) The method of claim 23, wherein the subject does not have a disorder disrupting normal calcium homeostasis or preventing calcium supplementation. ### Claim 39 (depends on 23) The method of claim 23 comprising administering a polymorph of (2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide). ### Claim 40 (depends on 23) The method of claim 23 comprising administering an amorphous form of (2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide). ### Claim 41 (depends on 23) The method of claim 23 comprising administering a lyophilized formulation of Compound 1, wherein the lyophilized formulation comprises Compound 1, a buffer and a bulking agent. ### Claim 42 (depends on 23) The method of claim 23, further comprising administering a therapeutically effective amount of a second active agent or a supportive care therapy. ### Claim 43 (depends on 23) The method of claim 23, wherein the subject is a patient 18 years or older.