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1. (WO2017096024) CYCLING THERAPY USING 3-(5-AMINO-2-METHYL-4-OXO-4H-QUINAZOLIN-3-YL)-PIPERIDINE-2,6-DIONE
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What is claimed is:

1. A method for treating, preventing, managing, and/or ameliorating lymphoma, while reducing an adverse effect associated with such treating, managing, and/or ameliorating, said method comprising administering to a patient in need thereof an effective amount of compound 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, which has the following


or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, stereoisomer, tautomer or racemic mixture thereof, wherein the compound is administered to said subject in a cycling therapy, said cycling therapy comprising:

(a) an administration period of 5 days followed by a rest period of 2 days; or

(b) an administration period of 21 days followed by a rest period of 7 days.

2. The method of claim 1, wherein the compound is a solvate of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione.

3. The method of claim 1, wherein the compound is a hydrate of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione.

4. The method of claim 1, wherein the compound is a pharmaceutically acceptable salt of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione.

5. The method of claim 1, wherein the compound is 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione.

6. The method of any of claims 1-5, wherein the cycling therapy comprises an administration period of 5 days followed by a rest period of 2 days.

7. The method of any of claims 1-5, wherein the cycling therapy comprises an administration period of 21 days followed by a rest period of 7 days.

8. The method of any one of claims 1 to 7, wherein the adverse effect comprises neutropenia.

9. The method of any of claims 1-8, wherein the compound is administered orally.

10. The method of any of claims 1-8, wherein the compound is administered at a dose of about 1 mg to about 5 mg.

11. The method of claim 10, wherein the dose is about 3 mg or about 4 mg.

12. The method of claim 10, wherein the dose is about 4 mg.

13. The method of claim 10, wherein the dose is about 3 mg.

14. The method of any one of claims 1 to 13, wherein the cycling therapy is repeated 2 to 6 times.

15. The method of any one of claims 1 to 14, wherein the method further comprises co-administering a second therapeutic agent.

16. The method of claim 15, wherein said second therapeutic agent is selected from oblimersen, GM-CSF, G-CSF, SCF, EPO, rituximab, obinutuzumab,

tositumomab,131I tositumomab, 90Y ibritumomab, 11 II ibritumomab, ofatumumab, brentuximab vedotin, nelarabine, cyclophosphamide, chlorambucil, bendamustine, carmustine, ifosfamide, prednisone, dexamethasone, cisplatin, carboplatin, oxaliplatin, fludarabine, pentostatin, cladribine, cytarabine, gemcitabine, methotrexate, pralatrexate, vincristine, vinblastine sulfate, doxorubicin, mitoxantrone, etoposide, belinostat, bortezomib, denileukin diftitox, ibrutinib, idelalisib, intron A, recombinant interferon Alfa-2b, romidepsin, lenalidomide, mechlorethamine hydrochloride, plerixafor, vorinostat, and bleomycin, or a combination thereof.

17. The method of any of claims 1 to 16, wherein the lymphoma is non-Hodgkin lymphoma.

18. The method of any of claims 1 to 17, wherein the lymphoma is diffuse large B-cell lymphoma.

19. The method of claim 18, wherein the diffuse large B-cell lymphoma is activated B-cell type.

20. The method of claim 18, wherein the diffuse large B-cell lymphoma is germinal center B-cell type.

21. The method of claim 18, wherein the diffuse large B-cell lymphoma is of unclassified cell of origin.

22. The method of any of claims 1 to 16, wherein the lymphoma is mantle cell lymphoma.

23. The method of any of claims 1 to 16, wherein the lymphoma is relapsed or refractory.

24. The method of claim 18, wherein the diffuse large B-cell lymphoma is relapsed or refractory.

25. A compound for use in a method for treating, preventing, managing, and/or ameliorating lymphoma in a subject, while reducing an adverse effect associated with such treating, managing, and/or ameliorating, wherein the compound is 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidin -2,6-dione, which has the following structure:


or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, stereoisomer, tautomer or racemic mixture thereof, and wherein said method comprises administering to a subject in need thereof an effective amount of said compound, wherein the compound is administered to said subject in a cycling therapy, said cycling therapy comprising:

(a) an administration period of 5 days followed by a rest period of 2 days; or

(b) an administration period of 21 days followed by a rest period of 7 days.

26. The compound for use of claim 1, wherein the compound is 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione; a solvate of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione; a hydrate of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione; or a pharmaceutically acceptable salt of 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione.

27. The compound for use of claims 25-26, wherein the cycling therapy comprises an administration period of 5 days followed by a rest period of 2 days; or wherein the cycling therapy comprises an administration period of 21 days followed by a rest period of 7 days.

28. The compound for use of any one of claims 25 to 27, wherein the adverse effect comprises neutropenia.

29. The compound for use of any of claims 24-28, wherein the compound is administered orally.

30. The compound for use of any of claims 24-28, wherein the compound is administered at a dose of about 1 mg to about 5 mg.

31. The compound for use of claim 30, wherein the dose is about 3 mg to about 4 mg; about 4 mg; or about 3 mg.

32. The compound for use of any one of claims 24 to 31, wherein the cycling therapy is repeated 2 to 6 times.

33. The compound for use of any one of claims 24 to 32, wherein the method further comprises co-administering a second therapeutic agent.

34. The compound for use of claim 33, wherein said second therapeutic agent is selected from oblimersen, GM-CSF, G-CSF, SCF, EPO, rituximab, obinutuzumab, tositumomab,131I tositumomab, 90Y ibritumomab, 11 II ibritumomab, ofatumumab, brentuximab vedotin, nelarabine, cyclophosphamide, chlorambucil, bendamustine, carmustine, ifosfamide, prednisone, dexamethasone, cisplatin, carboplatin, oxaliplatin, fludarabine, pentostatin, cladribine, cytarabine, gemcitabine, methotrexate, pralatrexate, vincristine, vinblastine sulfate, doxorubicin, mitoxantrone, etoposide, belinostat,

bortezomib, denileukin diftitox, ibrutinib, idelalisib, intron A, recombinant interferon Alfa-2b, romidepsin, lenalidomide, mechlorethamine hydrochloride, plerixafor, vorinostat, and bleomycin, or a combination thereof.

35. The compound for use of any of claims 24 to 34, wherein the lymphoma is

(i) non-Hodgkin lymphoma, preferably wherein the lymphoma is diffuse large B-cell lymphoma;

(ii) mantle cell lymphoma; or

(iii) relapsed or refractory.

36. The compound for use of any of claims 24 to 35, wherein the diffuse large B-cell lymphoma is activated B-cell type; germinal center B-cell type; of unclassified cell of origin; or relapsed or refractory.