Diffuse Large B Cell Lymphoma (DLBCL)
Conditions
Keywords
CAR T, CART, CAR-T, Cell therapy, Lymphoma, Diffuse large B cell lymphoma (DLBCL), Primary mediastinal (thymic) large B cell lymphoma (PMBCL), High-grade B cell lymphoma (HGBCL), Follicular lymphoma (FL) 3b, DLBCL transformed from FL, NHL, Non hodgkin's, Dual targeting, Gene edit, T cell, CD20, CD79a, CBLB, Non-hodgkin's, Non-hodgkin
Brief summary
This non-randomized, open label, multi-site, first-in-human, Phase 1/2 study CRC-403 will evaluate the safety and efficacy of bbT369 in subjects with relapsed and/or refractory B cell non-Hodgkin's lymphoma (NHL). A long-term follow-up (LTF-01 \[NCT06798298\]) is planned, in which subjects who received bbT369 will be followed for up to 15 years after drug product infusion to evaluate for safety and continued efficacy.
Detailed description
Former Sponsor 2seventy bio The trial was intended to be a Phase 1/2 trial, but no participants were enrolled in Phase 2, consequently the study was terminated in Phase 1.
Interventions
BIOLOGICALbbT369
bbT369 is a genetically modified autologous T cell immunotherapy product consisting of T cells that are transduced with a single lentiviral vector (LVV) to express anti-CD79a and anti-CD20 chimeric antigen receptors (CARs) and transfected with an mRNA encoding the CBLB-targeting megaTAL enzyme to edit the CBLB gene, suspended in a cryopreservative solution.
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥18 years of age at the time of signing informed consent. * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. * Diagnosis of B-cell NHL according to WHO 2017 classification or WHO 2016 classification where applicable: 1. DLBCL (germinal center B cell \[GCB\] or activated B cell \[ABC\] type or not otherwise specified \[NOS\]) 2. HGBCL (with MYC and BCL2 and/or BCL6 rearrangements or NOS) 3. PMBCL 4. FL 3b 5. DLBCL transformed from FL * Participants must have relapsed or refractory (r/r) B cell NHL after autologous stem cell transplant (ASCT) or at least 2 prior lines of therapy including an anti-CD20 monoclonal antibody and an anthracycline containing chemotherapy regimen. Note: participants with DLBCL transformed from FL must have r/r disease after ASCT or at least 2 prior therapies following transformation irrespective of therapeutic agents. * At least 1 FDG-avid lesion per Lugano Classification criteria at time of enrollment.
Exclusion criteria
* Treatment with any investigational cellular therapy prior to enrollment. Treatment with an approved anti-CD19 CAR T cell therapy in an investigational setting may be permitted after discussion with and approval of the Sponsor. * Progression within 6 weeks of prior anti-CD19 CAR T cell therapy. * Residual toxicities or end-organ damage to vital organs from prior therapy that could put a subject at undue risk based on Investigator's assessment. Toxicities related to prior cytokine release syndrome (CRS) or neurotoxicity must be resolved. * If a subject has received prior anti-CD19 CAR T therapy, development of ≥ Grade 3 CAR T related CRS or ≥ Grade 3 neurotoxicity that in the opinion of the Investigator would cause unacceptable risk of toxicity to the subject upon treatment with bbT369. * Primary central nervous system (CNS) lymphoma or a history or presence of clinically relevant CNS pathology. * Active autoimmune disease requiring systemic immunosuppressive and/or cytotoxic therapy within the past two years. * Treatment with any prior anti-CD79a therapy. * Previous history of an allogeneic bone marrow transplantation. Autologous stem cell transplantation (ASCT) is permitted.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1: Incidence of safety events including: adverse events (AEs), adverse events of special interest (AESIs), and dose limiting toxicities (DLTs) | Day 1 through Month 24 |
Secondary
| Measure | Time frame |
|---|---|
| Phase 1: Rates of disease-specific response criteria including complete response rate(CRR), partial response rate(PRR), stable disease rate(SDR), and progressive disease rate(PDR) according to the Lugano 2014 response criteria as assessed by Investigator | Day 1 through Month 24 |
| Phase 1: Overall Response Rate (ORR) according to the Lugano 2014 response criteria as assessed by Investigator | Day 1 through Month 24 |
| Phase 1: Time to response (TTR) | Day 1 through Month 24 |
| Phase 1: Time to complete response (TCR) | Day 1 through Month 24 |
| Phase 1: Time to next treatment for B Cell NHL (TTNT) | Day 1 through Month 24 |
Countries
United States
Outcome results
None listed