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EP-4739317-A1 - PRALATREXATE AND COP COMBINATION FOR THE TREATMENT OF PATIENTS WITH PERIPHERAL T CELL LYMPHOMA

EP4739317A1EP 4739317 A1EP4739317 A1EP 4739317A1EP-4739317-A1

Abstract

Methods for treating peripheral T-cell lymphoma include administering to a subject a combination of Cyclophosphamide, Vincristine, Prednisone, and Pralatrexate, wherein the combination does not include doxorubicin. The treatment may be administered in repeated three-week cycles, optionally including a drug holiday.

Inventors

  • ANVEKAR, Ashish

Assignees

  • Acrotech Biopharma Inc.

Dates

Publication Date
20260513
Application Date
20240705

Claims (20)

  1. CLAIMS 1. A method for treating peripheral T-cell lymphoma (PTCL) comprising administering to a subject in need thereof a combination comprising Cyclophosphamide, Vincristine, Prednisone and Pralatrexate, wherein the combination does not comprise doxorubicin.
  2. 2. The method according to claim 1, wherein the combination consists of Cyclophosphamide, Vincristine, Prednisone and Pralatrexate.
  3. 3. The method according to claim 1 or 2, wherein the administering occurs in a three- week cycle optionally comprising a drug holiday.
  4. 4. The method according to claim 3, wherein the Cyclophosphamide, Vincristine, Prednisone and Pralatrexate are independently administered daily, weekly, or once every two weeks for at most two weeks of the three-week cycle, such that the three-week cycle contains a weeklong drug holiday.
  5. 5. The method according to claim 3 or 4, wherein the three-week cycle is repeated from at least 1 to 10 times.
  6. 6. The method according to claim 5, wherein the three-week cycle is repeated one time, two times, three times, four times, five times, six times, seven times, eight times, nine times, or ten times.
  7. 7. The method according to any one of claims 1-6, wherein the Pralatextrate is administered on days 1 and 8 of a treatment cycle.
  8. 8. The method according to any one of claims 1-6, wherein the Cyclophosphamide and/or Vinicristine, and/or Predinisone is administered daily for a time period within the treatment cycle.
  9. 9. The method according to claim In another aspect, wherein the Cyclophosphamide and/or Vinicristine, and/or Predinisone is administered daily for days 1-15, or for days 1-10, or for days 1-8, or for days 1-6, or for days 1-5, or for days 1-4, or for days 1-3 of the treatment cycle.
  10. 10. The method of claim 1, wherein the method comprises a 21 day treatment cycle, the treatment cycle comprising: a) administering Pralatrexate in a dosage of at least about 10 mg/m 2 intravenously on day 1 and day 8; b) administering Cyclophosphamide in a dosage of at least about 700 mg/m 2 intravenously and Vincristine in a dosage of at least about 1 mg/m 2 intravenously, on day 1, wherein the Cyclophosphamide and/or Vinicristine are independently optionally administered following or concomitantly with the administration of Pralatrexate on day 1; and c) administering Prednisone in a dosage of at least about 50 mg orally on each of day 1 to day 5, wherein the prednisone is optionally administered on day 1 following the administration of Pralatrexate.
  11. 11. The method of claim 10, wherein the 21 day cycle is repeated between 1 to 6 times.
  12. 12. The method of claim 10 or 11, wherein the treatment cycle comprises at least one of: a) administering Pralatrexate in a dosage of about 20 to about 30 mg/m 2 intravenously on day 1 and day 8; b1) administering Cyclophosphamide in a dosage of from about 700 mg/m 2 to about 800 mg/m 2 on day 1; b2) administering Cyclophosphamide in a dosage of about 750 mg/ m 2 intravenously on day 1; b3) administering Vincristine in a dosage of from about 1 mg/m 2 to about 2 mg/m 2 intravenously on day 1, b4) administering Vinicristine in a dosage of about 1.2 mg/m 2 to about 1.6 mg/m 2 intravenously on day 1, b5) administering Vinicristine in a dosage of about 1.4 mg/m 2 , intravenously, on day 1, c1) administering Prednisone in a dosage of from about 50 mg to 150 mg on day 1 following administration of Pralatrexate; c2) administering Prednisone in a dosage of from about 80 mg to about 120 mg on day 1 following administration of Pralatrexate, and c3) administering Prednisone in a dosage of about 100 mg orally on day 1 following administration of Pralatrexate.
  13. 13. A kit comprising Pralatrexate, Cyclophosphamide, Vincristine, and Prednisone, wherein said kit does not comprise doxorubicin.
  14. 14. The kit of claim 13, wherein the Pralatrexate, is formulated separately from the Cyclophosphamide, the Vincristine, and the Prednisone.
  15. 15. The kit of claim 13, wherein the kit comprises a first pharmaceutical composition comprising about 20 to 30 mg/m 2 Pralatrexate and a first pharmaceutically acceptable excipient and/or a second pharmaceutical composition comprising about 500-1000 mg/m 2 Cyclophosphamide and a second pharmaceutically acceptable excipient, and/or a third pharmaceutical composition comprising about 1-3 mg/m 2 Vinicristine and a third pharmaceutically acceptable excipient, and/or a fourth pharmaceutical composition comprising about 50-150 mg Prednisone and a fourth pharmaceutically acceptable excipient.
  16. 16. The kit according to claim 15, wherein at least two of the first pharmaceutical composition, second pharmaceutical composition, third pharmaceutical composition and fourth pharmaceutical composition are the same pharmaceutical composition.
  17. 17. The kit of claim 15 or 16, wherein the first pharmaceutical composition is an intravenous composition.
  18. 18. The kit of any one of claims 15-17, wherein the second pharmaceutical composition is an intravenous composition.
  19. 19. The kit of any one of claims 15-18, wherein the third pharmaceutical composition is an intravenous composition.
  20. 20. The kit of any one of claims 15-19, wherein the fourth pharmaceutical composition is an oral composition.

Description

PRALATREXATE AND COP COMBINATION FOR THE TREATMENT OF PATIENTS WITH PERIPHERAL T CELL LYMPHOMA CROSS REFERENCE TO RELATED APPLICATIONS The present application claims priority to and the benefit of U.S. App. No. 63/525,585, filed July 7, 2023, which is hereby incorporated by reference in its entirety. BACKGROUND OF THE INVENTION Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The term “lymphomas” refers to a variety of disease states, including Non-Hodgkins Lymphoma (NHL); diffuse large B-cell lymphoma (DLBCL); follicular lymphoma (FL); Hodgkin’s Disease; Burkitt's Lymphoma; cutaneous T cell lymphoma; primary central nervous system lymphoma, and lymphomatous metastases. In most cases, lymphoma is characterized by the presence of cancerous B cells. However, in peripheral T cell lymphoma (PTCL), the disease state is characterized by the presence of cancerous T lymphocytes. Treatment approaches for PTCL have mirrored diffuse large B-cell lymphoma, although the majority of PTCLs have an inferior prognosis compared with their B-cell counterparts. Combination chemotherapy with CHOP (Cyclophosphamide, Hydroxydaunorubicin [Doxorubicin], Oncovin [Vincristine], and Prednisone) is the most commonly used first-line treatment and is considered the “standard therapy” despite its limited efficacy. Given this limited efficacy, improved methods of treatment for PTCL are urgently required. Andrei R. Shustov et al. (Blood (2016) 128 (22): 5355), which is hereby incorporated by reference in its entirety, discloses that Pralatrexate was the first drug approved in the US for the treatment of patients with relapsed or refractory PTCL (R/R PTCL). Pralatrexate is administered intravenously (IV) at a dose of 30 mg/m2 weekly for 6 weeks of a 7-week treatment cycle. Since pralatrexate and each of the components of the CHOP regimen target different aspects of tumor cell growth and proliferation, there is a potential for synergistic anti-tumor effect, and limited additive toxicities. Andrei R. Shustov et al. (Blood (2017) 130 (Supplement 1): 818) , which is hereby incorporated by reference in its entirety, discloses a Phase-I dose escalation study of Pralatrexate in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). In Part 1 of this 3+3 dose-escalation study, pralatrexate was administered at 10, 15, 20, 25, or 30 mg/m2 as an IV push on days 1 and 8 of a standard 21-day CHOP regimen ADMIN 688259591v1 (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2 [maximum 2 mg] on day 1 and oral prednisone 100 mg on days 1-5). In Part 2 of the study patients were treated at the MTD of pralatrexate established in Part 1, with standard CHOP. In both parts of the study patients were treated with up to 6 cycles of therapy, or until toxicity or disease progression. SUMMARY OF THE INVENTION The present disclosure provides compositions and methods for treating peripheral T- cell lymphoma featuring a combination of Pralatrexate, Cyclophosphamide, Vincristine, and Prednisone. In accordance with the present disclosure, T cell non-Hodgkin’s lymphoma is treated using a Pralatrexate and COP (Cyclophosphamide, Vincristine, and Prednisone) combination. Thus, in accordance with one aspect of the disclosure, a method is provided for the treatment of T cell non-Hodgkin’s lymphoma comprising administering to a patient suffering from lymphoma a therapeutically effective amount of Pralatrexate and COP (Cyclophosphamide, Vincristine, and Prednisone) combination. Methods for treating peripheral T-cell lymphoma (PTCL) are provided which may comprise administering to a subject in need thereof a combination comprising Cyclophosphamide, Vincristine, Prednisone and Pralatrexate, wherein the combination does not comprise doxorubicin. In some embodiments, the combination consists of Cyclophosphamide, Vincristine, Prednisone and Pralatrexate. In various implementations, the administering occurs in a three-week cycle optionally comprising a drug holiday (e.g., a period of time during the cycle wherein no or different drugs are administered). In various implementations, the Cyclophosphamide, Vincristine, Prednisone and Pralatrexate are independently administered daily, weekly, or once every two weeks for at most two weeks of the three-week cycle, such that the three-week cycle contains a weeklong drug holiday. In some embodiments, the three-week cycle is repeated from at least 1 to 10 times. For example, the three-week cycle is repeated one time, two times, three times, four times, five times, six times, seven times, eight times, nine times, or ten times. In some embodiments, the Pralatextrate is administered on days 1 and 8 of a treatment cycle. In certain aspects, the Cyclophosphamide and/or Vinicristine, and/or Predinisone is administered daily for a time period within the treatment cycle. In some embodiments, the Cyclophosphamide and/or Vinicristine, and/or Predinis