METHODS FOR THE TREATMENT AND MANAGEMENT OF MYELOPROLIFERATIVE DISEASES USING 4-(AMINO)-2-(2,6-DIOXO(3-PIPERIDYL)-ISOINDOLINE-1,3-DIONE IN COMBINATION WITH OTHER THERAPIES

• US 20090088410A1
• Filed: 12/05/2008
• Published: 04/02/2009
• Est. Priority Date: 11/06/2002
• Status: Active Grant

• Current Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Original Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Inventors: Zeldis, Jerome B.
• Granted Patent: US 8,034,831 B2
• Time in Patent Office: Days
• US Class Current: 514/171
• 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 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/724 Cyclodextrins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

Methods of treating, preventing and/or managing a myeloproliferative disease are disclosed. Specific methods encompass the administration of 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, in combination with a second active agent. Particular second active agents are is prednisone, JAK1 inhibitor, JAK2 inhibitor, FLT3 inhibitor, BCL2 inhibitor, and HDAC inhibitor.

Claims

1. A method of treating or managing a myeloproliferative disease, which comprises administering to a patient having a myeloproliferative disease from about 0.1 to about 10 mg per day of 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, and a therapeutically or prophylactically effective amount of at least one second active agent.

2. The method of claim 1, wherein the myeloproliferative disease is polycythemia rubra vera, primary thrombocythemia, myelofibrosis, myelofibrosis with myeloid metaplasia, or agnogenic myeloid metaplasia.

3. The method of claim 1, wherein the second active agent is prednisone, JAK1 inhibitor, JAK2 inhibitor, FLT3 inhibitor, BCL2 inhibitor, or HDAC inhibitor.

4. The method of claim 1, wherein the second active agent is prednisone, INCB018424, SB1518, XL019, TG101348, GX15-070MS or ITF2357.

5. The method of any one of claims 1 to 4, wherein the patient is refractory to a conventional myeloproliferative disease treatment.

6. The method of any one of claims 1 to 4, wherein the patient is refractory to a myeloproliferative disease treatment comprising thalidomide.

7. The method of any one of claims 1 to 4, wherein the second active agent is capable of suppressing the overproduction of hematopoietic stem cells or ameliorating one or more of the symptoms of a myeloproliferative disease.

8. The method of any one of claims 1 to 4, wherein the stereoisomer is an enantiomerically pure R isomer.

9. The method of any one of claims 1 to 4, wherein the stereoisomer is an enantiomerically pure S isomer.

10. The method of any one of claims 1 to 4, wherein the myeloproliferative disease is primary or secondary.

11. The method of any one of claims 1 to 4, wherein the compound is administered before, during or after transplanting umbilical cord blood, placental blood, peripheral blood stem cell, hematopoietic stem cell preparation or bone marrow into the patient.

12. The method of any one of claims 1 to 4, wherein the compound is administered orally.

13. The method of any one of claims 1 to 4, wherein the compound is administered in the form of a capsule or tablet.

14. The method of any one of claims 1 to 4, wherein the compound is administered cyclically.

15. The method of claim 14, wherein one cycle comprises four to six weeks.

16. The method of claim 15, wherein one cycle comprises the administration of the compound for 21 consecutive days followed by seven consecutive days of rest.

17. The method of claim 16, wherein the compound is administered in an amount of from about 0.1 to about 5 mg per day for 21 consecutive days followed by seven consecutive days of rest in a 28 day cycle.