Formulations of histone deacetylase inhibitor and uses thereof

Patent metadata

Field	Value
Publication number	US-10105552-B2
Application number	US-201615386834-A
Country	US
Kind code	B2
Filing date	Dec 21, 2016
Priority date	Apr 17, 2009
Publication date	Oct 23, 2018
Grant date	Oct 23, 2018

Abstract

Dosing regimens, methods of treatment, controlled release formulations, and combination therapies that include an HDAC inhibitor, or a pharmaceutically acceptable salt thereof, are described.

First claim

What is claimed is:

1. A method of treating cancer in a human patient, comprising:
administering to the patient a therapeutically effective amount of Compound 1:

or a pharmaceutically acceptable salt thereof; and
administering to the patient a therapeutically effective amount of rituximab.

2. The method of claim 1 , wherein the cancer is a hematological cancer, a solid tumor, or a sarcoma.

3. The method of claim 1 , wherein the cancer is selected from: breast cancer, colon cancer, colorectal carcinoma, non-small cell lung cancer, small-cell lung cancer, liver cancer, ovarian cancer, prostate cancer, uterine cervix cancer, urinary bladder cancer, gall bladder carcinoma, gastric carcinoma, esophageal cancer, gastrointestinal stromal tumor, pancreatic cancer, germ cell tumors, mast cell tumors, neuroblastoma, retinoblastoma, mesothelioma, mastocytosis, testicular cancers, glioblastomas, astrocytomas, sarcoma, osteosarcoma, B cell lymphoma, T cell lymphoma, NK cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, melanoma, basal cell carcinoma, skin cancer, myeloma, leukemia, acute myelocytic leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome, chronic lymphocytic leukemia (CLL) and chronic myelogenous leukemia (CML).

4. The method of claim 3 , wherein the cancer is a non-Hodgkin's lymphoma.

5. The method of claim 4 , wherein the cancer is an indolent non-Hodgkin's lymphoma.

6. The method of claim 1 , wherein the cancer is a kidney cancer.

7. The method of claim 6 , wherein the cancer is an adenocarcinoma of the kidney.

8. The method of claim 1 , wherein administering to the patient a therapeutically effective amount of Compound 1 comprises orally administering a first dose of Compound 1, and orally administering a second dose of Compound 1, wherein the two doses are administered within the same day.

9. The method of claim 8 , wherein the second dose is administered about 4 to about 6 hours after the first dose.

10. The method of claim 8 , wherein the first and second doses together comprise a total daily dose of from 10 mg/m 2 to 200 mg/m 2 of Compound 1.

11. The method of claim 10 , wherein the first dose is administered as a formulation that includes about 30 mg/m 2 , about 40 mg/m 2 , about 50 mg/m 2 , or about 60 mg/m 2 of Compound 1; and the second dose is administered as a formulation that includes about 30 mg/m 2 , about 40 mg/m 2 , about 50 mg/m 2 , or about 60 mg/m 2 of Compound 1.

12. The method of claim 10 , wherein the first and second doses together comprise a total daily dose of 30 mg/m 2 to 90 mg/m 2 of Compound 1.

13. The method of claim 12 , wherein the total daily dose is about 60 mg/m 2 or about 90 mg/m 2 of Compound 1.

14. The method of claim 8 , wherein administering a therapeutically effective amount of Compound 1 comprises maintaining an effective plasma concentration of the HDAC inhibitor for at least 6 consecutive hours.

15. The method of claim 8 , further comprising orally administering a third dose of Compound 1, wherein the first dose, the second dose and the third dose are administered consecutively about 4 to 6 hours apart.

Assignees

• Pharmacyclics Llc

Inventors

• Loury David J
• Buggy Joseph J
• Mody Tarak D
• Verner Erik J
• Purro Norbert
• Balasubramanian Sriram

Classifications

• A61K9/501

  Inorganic compounds · CPC title

• A61K47/02

  Inorganic compounds · CPC title

• A61K9/5026

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• A61K9/4808

  characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release (capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084) · CPC title

• A61K31/166

  having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol · CPC title