Golcadomide (BMS-986369) Post-CAR T-cell in R/R Aggressive Large B-cell Lymphoma Patients With High Risk of Relapse
This study is an open-label, multicenter, proof of concept, phase 2 trial. Patients will be recruited over 18 months. Safety analysis will be performed with a stop of the enrollment after 3 patients have either 1 complete treatment cycle or permanently discontinued treatment whichever occurs first. Approximatively 65 patients with aggressive large B-cell lymphoma (LBCL) (including diffuse large B-cell lymphoma (DLBCL), Primary mediastinal B-cell lymphoma (PMBCL), any transformed follicular or marginal zone lymphoma, high-grade B-cell lymphoma (HGBL)) will be enrolled in the study. The duration of treatment with golcadomide (CELMoD) is 24 weeks with 6 cycles of 28 days (4 weeks), starting at 5 days after CAR-T cells infusion. The primary objective of the study is to estimate the efficacy of golcadomide administered post-anti-CD19 CAR T-cell infusion, Efficacy determination will be based upon the primary endpoint of complete metabolic response (CMR) rate at 3 months after infusion of anti-CD19 CAR T-cell assessed by study investigator.
• Patient who understood and voluntarily signed and dated an informed consent prior to any study-specific assessments/procedures being conducted
• Adults patients (≥ 18-year-old at the time of signing the informed consent form; no upper age limit)
• Eligible for any commercialized market authorized anti-CD19 CAR T-cells
• Performance Status 0 or 1
• With aggressive large B-cell lymphoma, including:
‣ diffuse large B-cell lymphoma
⁃ Primary mediastinal B-cell lymphoma
⁃ Any transformed follicular or marginal zone lymphoma
⁃ high-grade B-cell lymphoma (HGBL) Note: patients with Central Nervous System (CNS) involvement could be included but not patients with primary CNS lymphoma
• Available biopsy for centralized review
• With a CAR T-cells indication as soon as 2nd line treatment no later than in 4th line, previously validated by the multidisciplinary tumor board Note: Any treatment performed prior to leukapheresis is considered a line of treatment
• Total MetabolicTumor Volume (TMTV) \> 80 ml, measured by centralized review, on 18FDG-PET (positron emission tomography) done just before starting CAR T-cells procedure (i.e., D-13 +/- 4 days before CAR-T cells infusion)
• Creatinine clearance (as estimated by Modification of Diet in Renal Disease (MDRD) if \> 60-year-old or Cockcroft-Gault if \<60yo) \>45 mL/min,
⁃ Adequate hepatic function:
∙ aspartate aminotransferase/alanine aminotransferase (ALT/AST) ≤ 3.0 x ULN. (Note: In the case of documented liver involvement by lymphoma, ALT/AST must be ≤ 5.0 x ULN)
‣ Serum total bilirubin ≤ 2.0 mg/dL (34 μmol/L) (Note: In the case of Gilbert's syndrome, or documented liver or pancreatic involvement by lymphoma, serum total bilirubin must be ≤ 3.0 mg/dL (51 μmol/L))
⁃ Patient covered by any social security system (France)
⁃ Patient who understands and speaks one of the country official languages, unless local regulation authorizes independent translators
⁃ Contraception:
∙ For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of \<1% per year, as soon as consent is signed, during the treatment period (including periods of treatment interruption), and for at least 28 days after the last dose of golcadomide, Women must refrain from donating eggs during this same period.