Compositions and Methods for Treating Patients Suffering from Glioma or Leukemia

Patent metadata

Field	Value
Publication number	US-2020054591-A1
Application number	US-201716346654-A
Country	US
Kind code	A1
Filing date	Nov 2, 2017
Priority date	Nov 2, 2016
Publication date	Feb 20, 2020
Grant date	—

Abstract

Pharmaceutical compositions, kits and methods for treating tumors such as glioma and cancers such as leukemia with (R)-2-hydroxyglutarate (R-2HG) are provided, along with therapeutic regimens including treatment of a patient suffering from glioma or leukemia with a MYC-signaling inhibitor followed by or cotemporaneous with treatment with R-2HG, and optionally other chemotherapeutic agents.

First claim

1 . A method of treating a tumor in a subject in need thereof comprising administering to the subject an effective amount of R-2-hydroxyglutarate (R-2HG).

2 . The method of claim 1 , wherein the tumor is a brain tumor.

3 . The method of claim 2 , wherein the tumor is a glioma.

4 . A method of treating cancer in a subject in need thereof comprising administering to the subject an effective amount of R-2HG.

5 . The method of claim 4 , wherein the cancer is selected from the group consisting of leukemia and brain cancer.

6 . The method according to claim 1 , further comprising administering at least one agent effective for inhibiting MYC signaling prior to administering the R-2HG.

7 . The method according to claim 6 , wherein the one or more agent is selected from the agents set forth in Table 4.

8 . The method according to claim 6 , wherein the patient is characterized by possessing a mutant form of IDH1 and/or an IDH2.

9 . The method according to claim 1 , further comprising administering one or more chemotherapeutic agents in conjunction with the R-2HG.

10 . The method according to claim 9 , wherein the one or more chemotherapeutic agents are selected from all trans retinoic acid (ATRA), azacitidine (AZA), daunorubicin, and decitabine.

11 . The method according to claim 1 , wherein the R-2HG comprises ester-modified R-2HG.

12 . A pharmaceutical composition comprising R-2HG and a pharmaceutically-acceptable carrier.

13 . The pharmaceutical composition of claim 12 , further comprising at least one agent that inhibits MYC signaling.

14 . The pharmaceutical composition according to claim 13 , wherein the at least one agent that inhibits MYC signaling is selected from the agents set forth in Table 4.

15 . The pharmaceutical composition according to claim 12 , wherein the R-2HG comprises recombinant R-2HG.

16 . The pharmaceutical composition according to claim 12 , wherein the R-2HG comprises ester-modified R-2HG.

17 . The pharmaceutical composition according to claim 12 , formulated as an injectable suspension.

18 . The pharmaceutical composition according to claim 17 , wherein the R-2HG is present in the suspension in a concentration of between about 10 μM and 500 μM, 50 μM and 400 μM, 100 μM and 300 μM, 150 μM and 250 μM, or about 200 μM R-2HG by weight, and is administered in a dose of about 1-10 mg R-2HG per kg body weight.

19 . A kit for treating a patient suffering from a glioma or leukemia, the kit comprising a first vial comprising R-2HG, and at least one second vial comprising an agent effective for inhibiting MYC signaling.

20 . The kit according to claim 19 wherein the at least one second vial comprises an agent selected from the group consisting of the agents set forth in Table 4.

Assignees

• Univ Cincinnati

Inventors

• Chen Jianjun
• Su Rui

Classifications

• A61K31/203

  Retinoic acids {; Salts thereof} · CPC title

• A61K31/706

  containing six-membered rings with nitrogen as a ring hetero atom · CPC title

• A61K31/225 Primary

  Polycarboxylic acids · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title