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An early phase, open label, multicentre, trial study to assess safety and efficacy of front-line therapy for EBV-associated Lymphomas 2 (TREBL-2) – ALLG NHL36

ACTRN 12622001189718

Brief Summary

The purpose of this study is to assess the safety and immune system response to treatment with Tislelizumab in patients with Epstein-Barr virus (EBV)–positive diffuse large B-cell lymphoma (DLBCL).

Intervention/Treatment

  • Drug: Tislelizumab
  • Drug: Rituximab
  • Drug: Cyclophosphamide
  • Drug: Doxorubicin
  • Drug: Vincristine
  • Drug: Prednisolone

Inclusion Criteria

  1. Local histological diagnosis (on core or excision biopsy) of de-novo systemic CD20+ EBV-associated DLBCL by EBER-ISH (positive is equals to or greater than 50% of lymphoma cells) without immunosuppression. (Immunosuppression includes lymphomas occurring after methotrexate, in patients with HIV, or following solid organ or haematopoietic stem cell transplant, and patients with inherited immunodeficiencies).
  2. Stages II-IV (or I with bulk equal to or greater than 7.5cm or systemic ‘B’ symptoms).
  3. Aged greater than 45 years.
  4. Adequate major organ function defined as:
    • ANC (segs + bands) equal to or greater than 1.0 x 10^9/L (can be supported by G-CSF).
    • Platelet count equal to or greater than 75 x 10^9/L (or 50 if bone marrow is involved).
    • Total bilirubin equal to or less than 1.5 x ULN (unless rise in bilirubin is due to Gilbert’s syndrome or of non-hepatic origin.
    • ALT and AST equal to or less than 3 x ULN.
    • Creatinine clearance equal to or greater than 30ml / min / 1.73m2 (Cockcroft-Gault formula).
    • LVEF within institutional normal limits (determined either by echocardiography or gated heart pool scan).
  5. ECOG status 0-2 (2 if related to lymphoma).
  6. Written informed consent.
  7. Life expectancy at least 3 months.
  8. Men who are sexually active with women of child-bearing potential, and women of child-bearing potential, must use any highly effective contraceptive method during the study (failure rate greater then 1% per year) and for a period of 120 days after the last dose of therapy. Should pregnancy occur during therapy or before 120 days, the treating physician should be informed immediately.
  9. PET/CT avid disease at baseline.
  10. Positive EBV IgG serology.
  11. Subjects must agree not to donate blood, semen or sperm while on study treatment and for least 120 days after treatment discontinuation.
  12. Subjects must agree not to share their medication and to return unused supplies.
  13. To take part in the PRO component of the study the subject must be able to read/write in English. Patients who do not meet this criteria can participate in the rest of the trial.

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