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
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.
1. A method of treating myelofibrosis with myeloid metaplasia, which comprises administering to a patient having myelofibrosis with myeloid metaplasia from about 0.1 to about 2.0 mg per day of 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione, or a pharmaceutically acceptable salt or stereoisomer thereof, and a therapeutically effective amount of prednisone.
2. The method of claim 1 , wherein the 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione is a free base.
3. The method of claim 1 , wherein the 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione is a pharmaceutically acceptable salt.
4. The method of claim 1 , wherein the 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione is a pharmaceutically acceptable stereoisomer.
5. The method of claim 4 , wherein the stereoisomer is an enantiomerically pure R isomer.
6. The method of claim 4 , wherein the stereoisomer is an enantiomerically pure S isomer.
7. The method of claim 1 , wherein the patient has bone marrow fibrosis.
8. The method of claim 1 , wherein the myelofibrosis with myeloid metaplasia is primary.
9. The method of claim 1 , wherein the myelofibrosis with myeloid metaplasia is secondary.
10. The method of claim 1 , wherein the 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione is administered before, during or after transplanting umbilical cord blood, placental blood, peripheral blood stem cells, a hematopoietic stem cell preparation or bone marrow into the patient.
11. The method of claim 1 , wherein the 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione is administered orally.
12. The method of claim 1 , wherein the 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione is administered in the form of a capsule.
13. The method of claim 1 , wherein the 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione is administered in the form of a tablet.
14. The method of claim 1 , wherein the 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione is administered cyclically.
15. The method of claim 14 , wherein one cycle comprises four to six weeks with a rest period of a week or two weeks.
16. A method of treating myelofibrosis with myeloid metaplasia, which comprises administering to a patient having myelofibrosis with myeloid metaplasia about 2.0 mg per day of 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione, and a therapeutically effective amount of prednisone.
17. The method of claim 16 , wherein the myelofibrosis with myeloid metaplasia is primary.
18. The method of claim 16 , wherein the myelofibrosis with myeloid metaplasia is secondary.
19. The method of claim 16 , wherein the patient is refractory to a conventional myeloproliferative disease treatment.
20. The method of claim 16 , wherein the patient has bone marrow fibrosis.
21. The method of claim 16 , wherein the 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione is administered orally.
22. The method of claim 16 , wherein the 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione is administered in the form of a capsule.
23. The method of claim 16 , wherein the 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione is administered in the form of a tablet.
24. The method of claim 16 , wherein the 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione is administered cyclically.
25. The method of claim 24 , wherein one cycle comprises four to six weeks with a rest period of a week or two weeks.
26. The method of claim 16 , wherein the 4-(amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione is administered before, during or after transplanting umbilical cord blood, placental blood, peripheral blood stem cells, a hematopoietic stem cell preparation or bone marrow into the patient.