A Phase II, Multicenter Study of GlOfitamab in Patients With Mantle Cell Lymphoma and inaDequate Response or Relapse Following CAR T-cell Therapy (GOLD)
This is a Phase 2, multicentre, single arm study that evaluates the efficacy and safety of glofitamab in MCL patients with inadequate response or relapse following CAR T-cell therapy.
• Able to provide written informed consent forms approved by the National Ethics Committee (NEC) prior to the initiation of any screening or study-specific procedures and able to understand and to comply with the requirements of the study and the schedule of assessments.
• Histologically confirmed MCL after CAR T-cells failure (CD20+ by flow cytometry or immunohistochemistry). Note: Availability of archival material is mandatory for the study to perform central pathology review. Central pathology confirmation is not required to start treatment.
• Age ≥ 18.
• Patients who received CAR T-cells therapy for R/R MCL at least 30 days prior to signing the informed consent form and who meet one of the following situations:
‣ Stable disease (SD) or progressive disease (PD) up to D+90; after CAR T-cells infusion (from D+30 to D+90);
⁃ Partial response (PR) at D+90 after CAR-T cells infusion;
⁃ Relapsed disease at any time after CAR-T cells infusion.
• No persistent CAR-T neurotoxicity symptoms or previous experience during CAR T-cells therapy of severe neurotoxicity grade \> 3
• Adverse events from prior anti-cancer therapy must have resolved to Grade ≤ 1 (hematological toxicities excepted).
• Adequate hematological counts are defined as follows:
‣ Absolute neutrophil count (ANC) \> 1.0 x 109/L unless due to bone marrow involvement by lymphoma;
⁃ Platelet count ≥ 50.000/mm3 unless due to bone marrow involvement by lymphoma;
⁃ Hemoglobin ≥ 8.0 g/dL.
• Adequate renal function defined as follows:
• \- Creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula).
• Adequate hepatic function per local laboratory reference range as follows (unless due to lymphoma):
‣ Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN;
⁃ Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin).
⁃ Participants must be able to adhere to the study visit schedule and other protocol requirements.
⁃ Life expectancy \> 12 weeks.
⁃ ECOG Performance Status of 0, 1, or 2.
⁃ Women of childbearing potential must have a negative pregnancy test at screening.
⁃ Women of childbearing potential must take necessary precautions to avoid pregnancy while receiving study treatments and for 2 months after the last dose of glofitamab, for 18 months after the last dose of obinutuzumab and for 3 months after the last dose of tocilizumab.
⁃ Male patient with a female partner of childbearing potential must agree to use an acceptable method of contraception for the duration of the study and for 2 months after the last dose of glofitamab, for 3 months after the last dose of obinutuzumab and for 2 months after the last dose of tocilizumab.