IP Library Granted Patent US 8,957,027
Granted Patent B2
US 8,957,027 · App. 11/759,471 · Granted Feb 17, 2015

Deacetylase inhibitor therapy

Inventors: William McCulloch (Raleigh, NC); Richard L. Piekarz (Silver Spring, MD); Susan E. Bates (Bethesda, MD)
Assignee: Celgene Corporation
A61K31/19A61K33/00A61K33/06A61K38/15
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Quick Facts
Patent No.
US 8,957,027
App. No.
11/759,471
Granted
Feb 17, 2015
Kind
B2
Abstract

The present invention relates to deacetylase inhibitor (e.g., histone deacetylase inhibitor) therapies and demonstrates that individuals with low electrolyte levels may have increased susceptibility to certain unwanted side effects such as cardiac side effects. In some embodiments, the invention provides methods of administering DAC or DAC inhibitor therapy that includes electrolyte supplementation.

Claims (27)

1. A method for treating a Hodgkin lymphoma, myeloma, or myelodysplastic syndrome in a patient comprising intravenously administering to the patient a unit dose of romidepsin over a time period of over 30 to 60 minutes.

2. The method of claim 1 , wherein the romidepsin is administered over a time period of over 30 to 50 minutes.

3. The method of claim 1 , wherein the romidepsin is administered over a time period of over 30 to 40 minutes.

4. The method of claim 1 , wherein the unit dosage form contains from 0.5 to 28 mg/m 2 of the romidepsin.

5. The method of claim 4 , wherein the unit dosage form of romidepsin is 8 mg/m 2 , or 10 mg/m 2 , or 12 mg/m 2 , or 13 mg/m 2 , or 14 mg/m 2 .

6. The method of claim 1 , wherein the romidepsin is administered on days 1, 8, and 15 of a 28-day cycle.

7. The method of claim 6 , wherein the 28-day cycle is repeated for 3-10 times.

8. A method for treating a Hodgkin lymphoma, myeloma, or myelodysplastic syndrome in a patient comprising the steps of:

intravenously administering romidepsin over a time period of over 30 to 60 minutes;

assessing serum potassium level in the patient;

assessing serum magnesium level in the patient;

administering potassium to the patient if the serum potassium concentration is below 3.5 mEq/L; and

administering magnesium to the patient if the serum magnesium concentration is below 1.9 mEq/L.

9. The method of claim 8 , wherein the step of administering potassium and/or magnesium occurs prior to initiation of the romidepsin therapy.

10. The method of claim 8 , wherein the step of administering potassium and/or magnesium occurs concurrently with initiation of the romidepsin therapy.

11. The method of claim 8 , wherein the step of administering potassium and/or magnesium occurs sequentially with initiation of the romidepsin therapy.

12. The method of claim 8 , wherein after administering potassium the serum potassium concentration in the patient reaches at least 3.5 mEq/L prior to initiation of the romidepsin therapy.

13. The method of claim 8 , wherein after administering magnesium the serum magnesium concentration in the patient reaches at least 1.9 mEq/L prior to initiation of the romidepsin therapy.

14. The method of claim 8 , wherein the romidepsin is administered as a unit dosage form.

15. The method of claim 14 , wherein the unit dosage form contains from 0.5 to 28 mg/m 2 of the romidepsin.

16. The method of claim 15 , wherein the unit dosage form of romidepsin is 8 mg/m 2 , or 10 mg/m 2 , or 12 mg/m 2 , or 13 mg/m 2 , or 14 mg/m 2 .

17. The method of claim 14 , wherein the romidepsin is administered on days 1, 8, and 15 of a 28-day cycle.

18. The method of claim 17 , wherein the 28-day cycle is repeated for 3-10 times.

19. The method of claim 8 , wherein the step of electrolyte supplementation results in mitigation of toxicities associated with the romidepsin therapy.

20. The method of claim 19 , wherein the toxicity is a cardiac toxicity.

21. The method of claim 8 , wherein the romidepsin is administered over a time period of over 30 to 50 minutes.

22. The method of claim 8 , wherein the romidepsin is administered over a time period of over 30 to 40 minutes.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 10, 2012
From: GLOUCESTER PHARMACEUTICALS, INC.
To: CELGENE CORPORATION
Reel/Frame 028020/0824 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 21, 2008
From: PIEKARZ, RICHARD L; BATES, SUSAN E
To: THE GOVERNMENT OF THE UNITED STATES OF AMERICA, REPRESENTED BY THE THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Reel/Frame 020683/0381 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 21, 2008
From: MCCULLOCH, WILLIAM
To: GLOUCESTER PHARMACEUTICALS
Reel/Frame 020683/0508 →
Continuity (3)
Provisional Application 60811961 · Jun 8, 2006
Provisional Application 60909780 · Apr 3, 2007
Related Publication 20080124403A1 · May 29, 2008