Method of treating bendamustine-responsive conditions in patients requiring reduced volumes for administration

Patent metadata

Field	Value
Publication number	US-9579384-B2
Application number	US-201514820291-A
Country	US
Kind code	B2
Filing date	Aug 6, 2015
Priority date	Mar 20, 2012
Publication date	Feb 28, 2017
Grant date	Feb 28, 2017

Abstract

Methods of treating bendamustine responsive conditions in patients having fluid and/or sodium intake restrictions are disclosed. The methods include identifying patients having such restrictions and in need of bendamustine, and then administering thereto a bendamustine-containing composition in a volume of about 120 ml or less intravenously over a period of about 15 minutes or less. The smaller volumes and reduced sodium load as compared to currently known methods of treatment minimize cardiac and/or renal stress in patients having diseases such as congestive heart failure or renal disease.

First claim

We claim:

1. A method of treating chronic lymphocytic leukemia or indolent B cell non-Hodgkin lymphoma in a subject comprising:
parenterally administering to the subject, over a period of less than or equal to about 15 minutes, a dose of from about 25 mg/m 2 to about 120 mg/m 2 of bendamustine or a pharmaceutically acceptable salt thereof, wherein said dose of bendamustine or pharmaceutically acceptable salt thereof is provided in a liquid composition comprising:
a total volume of about 100 ml or less;
bendamustine or a pharmaceutically acceptable salt thereof, at a concentration of from about 0.5 to about 5.6 mg/ml;

a solubilizer comprising polyethylene glycol and propylene glycol, wherein the amount of solubilizer is from about 0.5 to about 26.5% by volume;
a parenterally acceptable diluent; and optionally,
an antioxidant.

2. The method of claim 1 , wherein the subject is human.

3. The method of claim 1 , wherein the amount of solubilizer is from about 2.0 to about 22.4% vol.

4. The method of claim 1 , where the polyethylene glycol is PEG 400.

5. The method of claim 1 , wherein the concentration of bendamustine, or pharmaceutically acceptable salt thereof, in said liquid composition is from about 0.1 to about 3.2 mg/mL.

6. The method of claim 1 , wherein the weight ratio of polyethylene glycol to propylene glycol is about 90:10.

7. The method of claim 6 , wherein the volume of the liquid composition is about 50 ml.

8. The method of claim 1 , wherein the antioxidant is monothioglycerol.

9. The method of claim 1 , wherein the volume of the liquid composition is about 50 ml.

10. The method of claim 1 , wherein the subject is being treated for chronic lymphocytic leukemia.

11. The method of claim 10 , wherein the liquid composition is administered intravenously in a volume of about 50 ml over a period of 10 minutes or less on days 1 and 2 of a 28 day cycle.

12. The method of claim 11 , wherein the liquid composition is administered over a period of about 10 minutes.

13. The method of claim 11 , wherein the liquid composition is administered for up to 6 cycles.

14. The method of claim 10 , wherein said dose of bendamustine or pharmaceutically acceptable salt thereof is from about 25 mg/m 2 to about 100 mg/m 2 .

15. The method of claim 10 , wherein said dose of bendamustine or pharmaceutically acceptable salt thereof is about 100 mg/m 2 .

16. The method of claim 1 , wherein the subject is being treated for indolent B cell non-Hodgkin lymphoma.

17. The method of claim 16 , wherein the liquid composition is administered intravenously in a volume of about 50 ml over a period of about 10 minutes or less on days 1 and 2 of a 21 day cycle.

18. The method of claim 17 , wherein the liquid composition is administered over a period of about 10 minutes.

19. The method of claim 17 , wherein the composition is administered for up to 8 cycles.

20. The method of claim 16 , wherein said dose of bendamustine or pharmaceutically acceptable salt thereof is from about 60 mg/m 2 to about 120 mg/m 2 to the subject.

21. The method of claim 16 , wherein said dose of bendamustine or pharmaceutically acceptable salt thereof is about 120 mg/m 2 .

22. The method according to claim 1 , wherein the bendamustine is present as the hydrochloride salt.

23. A method of treating chronic lymphocytic leukemia or indolent B cell non-Hodgkin lymphoma in a subject consisting essentially of:
parenterally administering to the subject, over a period of less than or equal to about 15 minutes, a dose of from about 25 mg/m 2 to about 120 mg/m 2 of bendamustine or a pharmaceutically acceptable salt thereof, wherein said dose of bendamustine or pharmaceutically acceptable salt thereof is provided in a liquid composition comprising:
a volume of about 100 ml or less;
bendamustine or a pharmaceutically acceptable salt thereof, at a concentration of from about 0.5 to about 5.6 mg/ml;
a solubilizer comprising polyethylene glycol and propylene glycol, wherein the amount of solubilizer is from about 0.5 to about 26.5% by volume;
a parenterally acceptable diluent; and optionally,
an antioxidant.

Assignees

• Eagle Pharmaceuticals Inc

Inventors

• Sundaram Srikanth
• Tarriff Scott L

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P13/12

  of the kidneys · CPC title

• C07D235/12

  Radicals substituted by oxygen atoms · CPC title