Phase II study of the novel antifolate agent pralatrexate in combination with the histone deacetylase inhibitor romidepsin for the treatment of patients with mature T-cell lymphoma

Leuk Lymphoma. 2024 Jun;65(6):736-745. doi: 10.1080/10428194.2024.2329996. Epub 2024 Mar 22.

Abstract

Previously, we conducted a Phase I study of the combination of pralatrexate and romidepsin in patients with relapsed/refractory (R/R) lymphomas and subsequently conducted a multicenter Phase II study in patients with untreated or R/R mature T cell lymphomas (MTCL). Patients received pralatrexate 25 mg/m2 and romidepsin 12 mg/m2 every 2 weeks. Fourteen patients were evaluable for efficacy. Overall response rate was 35.7% with CR in 14.3% and disease control in 50%. The mDOR was 8.2 months, mPFS was 3.6 months, and mOS was 20.2 months. Gastrointestinal side effects were most common in up to 33%; there was only one hematologic toxicity of grade 3 anemia. Combining results of MTCL patients from the Phase I and II studies (N = 28), the ORR was 53.5% with CR in 21.4%, disease control in67.8%, and DOR of 7.2 months. The combination was safe however does not out-perform other combination strategies.Trial Registration: www.clinicaltrials.gov (NCT01947140).

Keywords: Chemotherapeutic approaches; T-cell lymphoma; antifolate; clinical results; epigenetics; lymphoma and Hodgkin disease.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aminopterin* / administration & dosage
  • Aminopterin* / adverse effects
  • Aminopterin* / analogs & derivatives
  • Aminopterin* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Depsipeptides* / administration & dosage
  • Depsipeptides* / adverse effects
  • Depsipeptides* / therapeutic use
  • Female
  • Folic Acid Antagonists / administration & dosage
  • Folic Acid Antagonists / adverse effects
  • Folic Acid Antagonists / therapeutic use
  • Histone Deacetylase Inhibitors* / administration & dosage
  • Histone Deacetylase Inhibitors* / adverse effects
  • Histone Deacetylase Inhibitors* / therapeutic use
  • Humans
  • Lymphoma, T-Cell* / drug therapy
  • Lymphoma, T-Cell* / pathology
  • Male
  • Middle Aged
  • Treatment Outcome

Substances

  • romidepsin
  • 10-propargyl-10-deazaaminopterin
  • Aminopterin
  • Depsipeptides
  • Histone Deacetylase Inhibitors
  • Folic Acid Antagonists

Associated data

  • ClinicalTrials.gov/NCT01947140