A Study of bbT369 in Relapsed and/or Refractory B Cell Non-Hodgkin's Lymphoma (NHL)
Study Details
Study Description
Brief Summary
A Phase 1/2 Study of bbT369, a dual targeting CAR T cell drug product with a gene edit, in Relapsed and/or Refractory B cell Non-Hodgkin's Lymphoma.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
This is a non-randomized, open label, multi-site Phase 1/2 study. This 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). Phase 1 will be a dose escalation, up to a planned four dose levels. After establishing MTD, Phase 2 will enroll subjects with B cell NHL in 2 cohorts: CAR T exposed subjects (Cohort 1) and CAR T naïve subjects (Cohort 2). A long-term follow-up 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: bbT369 Experimental Arm Open label, single arm treatment with bbT369 |
Biological: bbT369
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.
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Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
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≥18 years of age at the time of signing informed consent.
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Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
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Diagnosis of B-cell NHL according to WHO 2017 classification or WHO 2016 classification where applicable:
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DLBCL (germinal center B cell [GCB] or activated B cell [ABC] type or not otherwise specified [NOS])
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HGBCL (with MYC and BCL2 and/or BCL6 rearrangements or NOS)
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PMBCL
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FL 3b
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DLBCL transformed from FL
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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.
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At least 1 FDG-avid lesion per Lugano Classification criteria at time of enrollment.
Exclusion Criteria:
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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.
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Progression within 6 weeks of prior anti-CD19 CAR T cell therapy.
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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.
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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.
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Primary central nervous system (CNS) lymphoma or a history or presence of clinically relevant CNS pathology.
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Active autoimmune disease requiring systemic immunosuppressive and/or cytotoxic therapy within the past two years.
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Treatment with any prior anti-CD79a therapy.
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Previous history of an allogeneic bone marrow transplantation. Autologous stem cell transplantation (ASCT) is permitted.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Colorado Blood Cancer Institute | Denver | Colorado | United States | 80218 |
2 | Sarah Cannon | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- 2seventy bio
Investigators
- Study Director: Anna Truppel-Hartmann, MD, 2seventy bio, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CRC-403