GOLCADOMIDE for Relapsed or refractory aggressive large B-cell lymphoma

Inclusion criteria

• {"criterion_text":"- Patient who understood and voluntarily signed and dated an informed consent prior to any study-specific assessments/procedures being conducted\n- Adequate hepatic function: 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))\n- Patient covered by any social security system (France)\n- Patient who understands and speaks one of the country official languages, unless local regulation authorizes independent translators\n- 13.\tContraception (refer to section 14.7): •\tFor women of childbearing potential (WOCP): Agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one highly effective method, 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. •\tFor men: during the treatment period (including periods of treatment interruption) and for at least 28 days after the last dose of golcadomide, male subjects must: o\tWith female partners of childbearing potential: use a condom associated to a highly effective method of contraception or remain abstinent (refrain from heterosexual intercourse) o\tWith pregnant female partners: use a condom or remain abstinent (refrain from heterosexual intercourse) Men must refrain from donating sperm during this same period.\n- Adult patients (≥ 18-year-old at the time of signing the informed consent form; no upper age limit)\n- Eligible for any commercialized market authorized anti-CD19 CAR T-cells\n- PS 0, 1 or 2\n- With aggressive large B-cell lymphoma, including: •\tdiffuse large B-cell lymphoma •\tPrimary mediastinal B-cell lymphoma •\tAny transformed follicular or marginal zone lymphoma •\thigh-grade B-cell lymphoma (HGBL) Note: patients with CNS involvement could be included but not patients with primary CNS lymphoma\n- Available biopsy for centralized review Note: if several previous biopsies exist, the last one will be the one to be transmitted. If this biopsy has already been reviewed by LYSARC, the result of this review can be used for this patient\n- 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 and in compliance with marketing authorization\n- TMTV > 80 ml, measured by centralized review, on standard 18FDG-PET (positron emission tomography) done just before starting CAR-T procedure (i.e., before lymphodepletion)\n- Creatinine clearance (as estimated by MDRD if > 60-year-old or Cockcroft-Gault if <60yo > 45 mL/min"}

Exclusion criteria

• {"criterion_text":"- History of malignancy other than non-melanoma skin cancer or carcinoma in situ (eg, cervix, bladder, breast) unless disease free for at least 3 years\n- Pregnant, planning to become pregnant or lactating WOCBP (See definition section 14.6.1.1)\n- Any significant medical conditions, laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator’s decision)\n- Person deprived of his/her liberty by a judicial or administrative decision\n- Person hospitalized without consent\n- Adult person under legal protection\n- Any significant medical conditions, laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator’s decision)\n- Person deprived of his/her liberty by a judicial or administrative decision\n- Person hospitalized without consent\n- Adult person under legal protection\n- Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management; simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the sponsor’s medical monitor\n- History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection; subjects with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America guidelines or applicable country guidelines\n- History of allogeneic stem cell transplant complicated or not with active acute or chronic GVHD.\n- Current treatment with strong CYP3A4/5 modulators (see appendix 13)"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Complete metabolic response (CMR) rate at 3 months after anti-CD19 CAR T-cell infusion as assessed by the study investigator."}

Secondary endpoints

• {"endpoint_text":"- Objective response rate (ORR)","definition_or_measurement_approach":"ORR is defined as the incidence of either a complete (CMR) or a partial (PMR) metabolic response per the Lugano Classification (Cheson 2014) as determined by study investigators at 1 month, 3 months, 6 months, 1 year and 2 years from CAR-T infusion."}
• {"endpoint_text":"- Complete metabolic response (CMR)","definition_or_measurement_approach":"CMR assessed at specified timepoints (1 month, 3 months, 6 months, 1 year, and 2 years) per Lugano Classification (Cheson 2014)."}
• {"endpoint_text":"- Partial metabolic response (PMR)","definition_or_measurement_approach":"PMR assessed at specified timepoints (1 month, 3 months, 6 months, 1 year, and 2 years) per Lugano Classification (Cheson 2014)."}
• {"endpoint_text":"- Duration of response (DoR)","definition_or_measurement_approach":"Duration of response measured from time of documented response until disease progression or death."}
• {"endpoint_text":"- Event-free survival (EFS)","definition_or_measurement_approach":"EFS including earlier date of progression, start of subsequent new anti-lymphoma therapy including Stem Cells Transplant (SCT), or death from any cause."}
• {"endpoint_text":"- Progression-free survival (PFS)","definition_or_measurement_approach":"PFS defined from CAR T-cells infusion date to the date of disease progression per the Lugano Classification (Cheson 2014) or death from any cause."}
• {"endpoint_text":"- Time to next anti-lymphoma therapy (TTNLT)","definition_or_measurement_approach":"Time to next anti-lymphoma therapy including SCT (except SCT done as consolidation post-CART)."}
• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":"Overall survival measured from infusion date to death from any cause."}

France

Earliest CTIS Part Ii Submission Date

04-03-2024

Latest Decision Or Authorization Date

20-04-2026

Processing Time Days

777

Number Of Sites

13

Number Of Participants

61

Primary sponsor

Full Name

Lymphoma Academic Research Organisation

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France