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BiCAR Therapy - A Phase II Trial Evaluating Glofitamab, a Bispecific CD3xCD20 Antibody for Relapse/Refractory Lymphomas after CAR T-cells therapy
EU CTIS ID: 2023-508301-25-00
What this study is testing
The primary objective of the study is to assess the anti-lymphoma activity of glofitamab, a bispecific CD3xCD20 monoclonal antibody in patients with relapse/refractory (R/R) DLBCL (cohort 1) disease after anti-CD19 CAR T-cells therapy.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 1. Patients who received CAR T-cells therapy for R/R DLBCL (cohort 1) or R/R PMBL, mantle cell lymphoma, t-iNHL or iNHL (cohort 2), at least 1 month ago
- 10. Adequate liver function: Total bilirubin ≤ 1.5 x ULN; Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x ULN Note: Patients with documented history of Gilbert’s Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible)
- 11. Adequate hematological function: Neutrophil count of ≥ 1.0 G/L; Platelet count of ≥ 50 G/L (and platelet transfusion free within 14 days prior to administration of obinutuzumab); Hemoglobin (Hb) ≥ 8.0 g/dL (transfusion free within 21 days prior to administration of obinutuzumab) Note: patients who do not meet the above hematologic criteria, due to extensive tumor involvement in the marrow may be enrolled into the trial after the demonstration of involvement and consultation with the LYSARC. Please consult the LYSARC on the need for transfusion support within 21 days of obinutuzumab.
- 12. Adequate renal function: creatinine clearance (CrCl) calculated by MDRD/Cockroft-Gault formula of ≥ 30 mL/min 13.
- 13. Negative serum or urinary pregnancy test within 7 days prior to study treatment in women of childbearing potential.
- 14. Negative serologic or PCR test results for acute or chronic HBV infection. Note: Patients whose HBV infection status cannot be determined by serologic test results must be negative for HBV by PCR to be eligible for study participation.
You likely can't join if
- Previously known CD20 negative status, excepted if a new biopsy for cohort 1 or biopsy or cytometry analysis for cohort 2 proving a CD20 positive status is available before enrollment
- LVEF < 40% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan or significant cardiovascular disease such as New York Heart Association Class III or IV or Objective Class C or D cardiac disease (see appendix 16), myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina
- Any serious active disease or co-morbid medical condition
- Clinically significant history of liver disease or cirrhosis
- Prior history of malignancies other than lymphoma unless the subject has been free of the disease for ≥ 3 years. Exceptions will be allowed for patients with non-melanoma skin tumors (basal cell or squamous cell carcinoma of the skin) or any surgically removed stage 0 (in situ) carcinoma
- Prior solid organ transplantation.
See the full eligibility criteria
Who can join
- 1. Patients who received CAR T-cells therapy for R/R DLBCL (cohort 1) or R/R PMBL, mantle cell lymphoma, t-iNHL or iNHL (cohort 2), at least 1 month ago
- 10. Adequate liver function: Total bilirubin ≤ 1.5 x ULN; Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x ULN Note: Patients with documented history of Gilbert’s Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible)
- 11. Adequate hematological function: Neutrophil count of ≥ 1.0 G/L; Platelet count of ≥ 50 G/L (and platelet transfusion free within 14 days prior to administration of obinutuzumab); Hemoglobin (Hb) ≥ 8.0 g/dL (transfusion free within 21 days prior to administration of obinutuzumab) Note: patients who do not meet the above hematologic criteria, due to extensive tumor involvement in the marrow may be enrolled into the trial after the demonstration of involvement and consultation with the LYSARC. Please consult the LYSARC on the need for transfusion support within 21 days of obinutuzumab.
- 12. Adequate renal function: creatinine clearance (CrCl) calculated by MDRD/Cockroft-Gault formula of ≥ 30 mL/min 13.
- 13. Negative serum or urinary pregnancy test within 7 days prior to study treatment in women of childbearing potential.
- 14. Negative serologic or PCR test results for acute or chronic HBV infection. Note: Patients whose HBV infection status cannot be determined by serologic test results must be negative for HBV by PCR to be eligible for study participation.
- 15. Negative test results for HCV and HIV. Note: Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation.
- 16. Patients must agree to either remain completely abstinent or to use two effective contraceptive methods until: - If the patient is a male: at least 3 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, whichever is longer Men must refrain from donating sperm during this same period - If patient is a female of childbearing potential: until at least 18 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, whichever is longer
- 17. Patient must be willing and able to comply with protocol-mandated hospitalization upon administration of the first dose of glofitamab. Patient must also be willing to comply with all study-related procedures.
- 18. Signed written informed consent
- 19. Life expectancy ≥ 3 months
- 2. Patients who are not at least in partial metabolic response from 1 month after CAR T-cells infusion (i.e no metabolic response or first metabolic progressive disease or first relapse from 1 month after CAR T-cells infusion)
- 20. Patient covered by any social security system
- 21. Patient who understands and speaks one of the country official languages
- 22. Patient with a vaccination status in line with French National guidelines/recommendations (COSV, ANRS MIE)
- 23. Patient must agree to perform a SARS-CoV-2 PCR test within 48 hours prior administration of obinutuzumab, then C2 and each subsequent cycle of glofitamab
- 3. First metabolic progression, first relapse or no metabolic response after CAR T-cells infusion must be confirmed by PET-CT central review for enrollment
- 4. DLBCL with demonstrated lymphoma cells-expressing CD20 at relapse post CAR T-cells as demonstrated by biopsy before enrollment (cohort 1 only)
- 5. Aged 18 years or more with no upper age limit
- 6. ECOG performance status 0 or 1
- 7. Bi-dimensionally measurable disease defined by at least one single node or tumor lesion > 1.5 cm assessed by CT scan, or PET-CT with at least one hypermetabolic lesion
- 8. No persistant CAR-T neurotoxicity symptoms or previous experience during CAR T-cells therapy of neurotoxicity grade > 3
- 9. Adverse events from prior anti-cancer therapy must have resolved to Grade ≤ 1 (hematological toxicities excepted)
What rules you out
- Previously known CD20 negative status, excepted if a new biopsy for cohort 1 or biopsy or cytometry analysis for cohort 2 proving a CD20 positive status is available before enrollment
- LVEF < 40% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan or significant cardiovascular disease such as New York Heart Association Class III or IV or Objective Class C or D cardiac disease (see appendix 16), myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina
- Any serious active disease or co-morbid medical condition
- Clinically significant history of liver disease or cirrhosis
- Prior history of malignancies other than lymphoma unless the subject has been free of the disease for ≥ 3 years. Exceptions will be allowed for patients with non-melanoma skin tumors (basal cell or squamous cell carcinoma of the skin) or any surgically removed stage 0 (in situ) carcinoma
- Prior solid organ transplantation.
- Prior allogeneic SCT
- Autologous SCT within 100 days prior to obinutuzumab infusion
- Current uncontrolled autoimmune disease Note: History of autoimmune disease currently controlled and stable is acceptable for such therapy. See detailed description in paragraphe 8.2
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug.
- Major surgery or significant traumatic injury < 28 days prior to the obinutuzumab infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
- Patients with CLL, Richter and Burkitt lymphoma.
- Administration of a live, attenuated vaccine within 4 weeks before obinutuzumab infusion
- Treatment between infusion of CAR T-cells and pre-phase (i.e. obinutuzumab infusion on C1/D-3): with standard radiotherapy, systemic immunotherapeutic agents, any chemotherapeutic agent, any systemic immunosuppressive medications or treatment with any other investigational anti-cancer agent (defined as treatment for which there is currently no regulatory authority approved indication). Note: with the exception of corticosteroid treatment < 25 mg/day prednisone or equivalent. Inhaled and topical steroids are permitted
- Patient with history of confirmed progressive multifocal leukoencephalopathy (PML).
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
- History of illicit drug or alcohol abuse within 12 months prior to enrollment
- Person deprived of his/her liberty by a judicial or administrative decision
- Inability to comply with protocol mandated hospitalization and restrictions.
- Adult person under legal protection
- Adult person unabled to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness
- Pregnant or breast-feeding or intending to become pregnant during the study.
- Patients relapsing or progressing within 1 month after CAR T-cells therapy
- History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows: - Grade ≥ 3 adverse events with the exception of Grade 3 endocrinopathy managed with replacement therapy - Grade 1-2 adverse events that did not resolve to baseline after treatment discontinuation
- Current or past history of detectable cerebrospinal fluid lymphoma cells, or with a history of CNS lymphoma localization or primary CNS lymphoma.
- Current or past history of cerebral disorders
- Any serious psychiatric illness that would prevent the subject from signing the informed consent form
- Patients with history of macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH)
- Patients with known acute infection or reactivation of a latent infection, whether bacterial, viral (including, but not limited to, EBV, cytomegalovirus (CMV), hepatitis B, hepatitis C, and HIV), fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) in 2 week prior to enrollment.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.