A phase II Japanese trial of fludarabine, cyclophosphamide and rituximab for previously untreated chronic lymphocytic leukemia

Jpn J Clin Oncol. 2021 Mar 3;51(3):408-415. doi: 10.1093/jjco/hyaa215.

Abstract

Objective: Fludarabine, cyclophosphamide and rituximab (FCR) is the standard regimen for fit patients with untreated CD20-positive chronic lymphocytic leukemia (CLL). However, this combination is unavailable in Japan because rituximab is not approved for CLL. We investigated the efficacy and safety of FCR in this single-arm, multicenter study designed as a bridging study to the CLL8 study by the German CLL Study Group.

Methods: The study enrolled previously untreated patients with CLL of Binet stage B or C with active disease. Patients with a Cumulative Illness Rating Scale score of ≤6 and creatinine clearance of ≥70 ml/min were eligible. Patients received 6 cycles of FCR every 28 days and were followed for up to 1 year.

Results: Seven patients were enrolled. The best overall response rate according to the 1996 NCI-WG Guidelines, the primary endpoint of the study, was 71.4% (95% confidence interval, 29.0-96.3%), with one patient achieving complete response. No deaths or progression occurred during follow-up. The main adverse event was hematotoxicity. CD4-positive T-cell count decreased in all patients; most patients showed no reduction in serum immunoglobulin G.

Conclusion: Although the number of patients was limited, FCR appears to be effective with manageable toxicity for treatment-naïve fit Japanese patients with CD20-positive CLL.

Clinical trial number: JapicCTI-132285.

Keywords: FCR; chronic lymphocytic leukemia; phase II clinical trial; rituximab.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Aged
  • Antibodies, Neoplasm / immunology
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Area Under Curve
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / pharmacokinetics
  • Cyclophosphamide / therapeutic use*
  • Disease Progression
  • Endpoint Determination
  • Female
  • Humans
  • Immunosuppression Therapy
  • Japan
  • Leukemia, Lymphocytic, Chronic, B-Cell / blood
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Male
  • Middle Aged
  • Remission Induction
  • Rituximab / adverse effects
  • Rituximab / blood
  • Rituximab / pharmacokinetics
  • Rituximab / therapeutic use*
  • Treatment Outcome
  • Vidarabine / adverse effects
  • Vidarabine / analogs & derivatives*
  • Vidarabine / pharmacokinetics
  • Vidarabine / therapeutic use

Substances

  • Antibodies, Neoplasm
  • Rituximab
  • Cyclophosphamide
  • Vidarabine
  • fludarabine