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

Dai Maruyama, Hirokazu Nagai, Yoshinobu Maeda, Takahiko Nakane, Tatsu Shimoyama, Tomonori Nakazato, Rika Sakai, Takayuki Ishikawa, Koji Izutsu, Ryuzo Ueda, Kensei Tobinai

Research output: Contribution to journalArticle

5 Citations (Scopus)

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).

Original languageEnglish
JournalCancer Science
DOIs
Publication statusAccepted/In press - 2017

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Peripheral T-Cell Lymphoma
Mucositis
Lymphopenia
Thrombocytopenia
Anemia
Pharmacokinetics
Folic Acid Antagonists
Liver Function Tests
Leukopenia
Vitamin B 12
Neutropenia
Folic Acid
Disease-Free Survival
10-propargyl-10-deazaaminopterin
Therapeutics
Safety
Survival
Pharmaceutical Preparations
Population

Keywords

  • Clinical trial
  • Folic acid antagonists
  • Japanese
  • Peripheral T-cell lymphoma
  • Pralatrexate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase I/II study of pralatrexate in Japanese patients with relapsed or refractory peripheral T-cell lymphoma. / Maruyama, Dai; Nagai, Hirokazu; Maeda, Yoshinobu; Nakane, Takahiko; Shimoyama, Tatsu; Nakazato, Tomonori; Sakai, Rika; Ishikawa, Takayuki; Izutsu, Koji; Ueda, Ryuzo; Tobinai, Kensei.

In: Cancer Science, 2017.

Research output: Contribution to journalArticle

Maruyama, D, Nagai, H, Maeda, Y, Nakane, T, Shimoyama, T, Nakazato, T, Sakai, R, Ishikawa, T, Izutsu, K, Ueda, R & Tobinai, K 2017, 'Phase I/II study of pralatrexate in Japanese patients with relapsed or refractory peripheral T-cell lymphoma', Cancer Science. https://doi.org/10.1111/cas.13340
Maruyama, Dai ; Nagai, Hirokazu ; Maeda, Yoshinobu ; Nakane, Takahiko ; Shimoyama, Tatsu ; Nakazato, Tomonori ; Sakai, Rika ; Ishikawa, Takayuki ; Izutsu, Koji ; Ueda, Ryuzo ; Tobinai, Kensei. / Phase I/II study of pralatrexate in Japanese patients with relapsed or refractory peripheral T-cell lymphoma. In: Cancer Science. 2017.
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AU - Maruyama, Dai

AU - Nagai, Hirokazu

AU - Maeda, Yoshinobu

AU - Nakane, Takahiko

AU - Shimoyama, Tatsu

AU - Nakazato, Tomonori

AU - Sakai, Rika

AU - Ishikawa, Takayuki

AU - Izutsu, Koji

AU - Ueda, Ryuzo

AU - Tobinai, Kensei

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N2 - 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).

AB - 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).

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