Phase I/II study of pralatrexate in Japanese patients with relapsed or refractory peripheral T-cell lymphoma

Cancer Sci. 2017 Oct;108(10):2061-2068. doi: 10.1111/cas.13340. Epub 2017 Sep 4.

Abstract

Pralatrexate is a novel antifolate approved in the USA for the treatment of relapsed or refractory peripheral T-cell lymphoma. To assess its safety, efficacy, and pharmacokinetics in Japanese patients with this disease, we undertook a phase I/II study. Pralatrexate was given i.v. weekly for 6 weeks of a 7-week cycle. All patients received concurrent vitamin B12 and folic acid. In phase I, three patients received pralatrexate 30 mg/m2 and none experienced a dose-limiting toxicity. In phase II, we treated 22 additional patients with that dose. The median number of treatment cycles was 1 (range, 1-9). Nine of 20 evaluable patients (45%) achieved an objective response by central review, including two complete responses. All responses occurred within the first treatment cycle. At the time of data cut-off, median progression-free survival was 150 days. Median overall survival was not reached. In the total population, the most commonly reported adverse events included mucositis (88%), thrombocytopenia (68%), liver function test abnormality (64%), anemia (60%), and lymphopenia (56%). Grade 3/4 adverse events included lymphopenia (52%), thrombocytopenia (40%), leukopenia (28%), neutropenia (24%), anemia (20%), and mucositis (20%). The pharmacokinetic profile showed no drug accumulation with repeat dosing. These results indicate that pralatrexate is generally well tolerated and effective in Japanese patients with relapsed or refractory peripheral T-cell lymphoma. This trial was registered with ClinicalTrials.gov (NCT02013362).

Keywords: Clinical trial; Japanese; folic acid antagonists; peripheral T-cell lymphoma; pralatrexate.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aminopterin / administration & dosage
  • Aminopterin / adverse effects
  • Aminopterin / analogs & derivatives*
  • Aminopterin / pharmacokinetics
  • Drug Administration Schedule
  • Female
  • Folic Acid / administration & dosage*
  • Folic Acid / therapeutic use
  • Humans
  • Japan
  • Lymphoma, T-Cell, Peripheral / drug therapy*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Survival Analysis
  • Treatment Outcome
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 12 / therapeutic use

Substances

  • 10-propargyl-10-deazaaminopterin
  • Folic Acid
  • Aminopterin
  • Vitamin B 12

Associated data

  • ClinicalTrials.gov/NCT02013362