Diffuse Large B Cell Lymphoma (DLBCL)Phase 1NCT05169489
A Study of bbT369 in Relapsed and/or Refractory B Cell Non-Hodgkin's Lymphoma (NHL)
A Phase 1 study testing bbT369 in people with Diffuse Large B Cell Lymphoma (DLBCL), run by Regeneron Pharmaceuticals at 4 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B Cell Lymphoma (DLBCL)
- What is being tested?
- bbT369
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 4 sitesUnited States
- Study dates
- 24 Jan 2022to 19 Sep 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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:
- DLBCL (germinal center B cell [GCB] or activated B cell [ABC] type or not otherwise specified [NOS])
- HGBCL (with MYC and BCL2 and/or BCL6 rearrangements or NOS)
- PMBCL
Show all 10Show fewer
- FL 3b
- 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.
Who cannot join
- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Colorado Blood Cancer Institute
Denver, Colorado, 80218
Sarah Cannon
Nashville, Tennessee, 37203
Stanford Cancer Institute
Stanford, California, 94305
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: 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 (NHL)
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.
Read the 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.
- Conditions
- Diffuse Large B Cell Lymphoma (DLBCL)
- Being tested
- bbT369
- 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
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bbT369Biological
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.
| Study group | Role | What they receive |
|---|---|---|
| bbT369 Experimental Arm | Experimental | Open label, single arm treatment with bbT369 Receives: Biological: bbT369 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Incidence of safety events including: adverse events (AEs), adverse events of special interest (AESIs), and dose limiting toxicities (DLTs)
Measured: Day 1 through Month 24
Secondary outcomes (5)
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
Measured: Day 1 through Month 24
Phase 1: Overall Response Rate (ORR) according to the Lugano 2014 response criteria as assessed by Investigator
Measured: Day 1 through Month 24
Phase 1: Time to response (TTR)
Measured: Day 1 through Month 24
Phase 1: Time to complete response (TCR)
Measured: Day 1 through Month 24
Phase 1: Time to next treatment for B Cell NHL (TTNT)
Measured: Day 1 through Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2021
- Study start24 Jan 2022
- Primary completion19 Sep 2025
- Study completion19 Sep 2025
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B Cell Lymphoma (DLBCL)Studies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05169489
- Sponsor's protocol ID
- CRC-403
- Status last verified
- Oct 2025
- First submitted
- 11 Dec 2021
- Last updated
- 21 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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 (NHL)
- ClinicalTrials.gov ID
- NCT05169489
- Acronym / sponsor ID
- CRC-403
- Conditions
- Diffuse Large B Cell Lymphoma (DLBCL)
- 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)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 24 Jan 2022 (actual)
- Primary completion
- 19 Sep 2025 (actual)
- Study completion
- 19 Sep 2025 (actual)
- First posted
- 27 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| bbT369 Experimental Arm | Experimental | Biological: bbT369Open label, single arm treatment with bbT369 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- ≥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:
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bbT369bbT369 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. | Biological | bbT369 Experimental Arm |
Primary outcome
Phase 1: Incidence of safety events including: adverse events (AEs), adverse events of special interest (AESIs), and dose limiting toxicities (DLTs)
Time frame: Day 1 through Month 24
5 secondary outcomes
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
Time frame: Day 1 through Month 24
Phase 1: Overall Response Rate (ORR) according to the Lugano 2014 response criteria as assessed by Investigator
Time frame: Day 1 through Month 24
Phase 1: Time to response (TTR)
Time frame: Day 1 through Month 24
Phase 1: Time to complete response (TCR)
Time frame: Day 1 through Month 24
Phase 1: Time to next treatment for B Cell NHL (TTNT)
Time frame: Day 1 through Month 24
Results and safety
The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2025.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trial Management study director
Regeneron Pharmaceuticals
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing bbT369 in people with Diffuse Large B Cell Lymphoma (DLBCL), run by Regeneron Pharmaceuticals at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Incidence of safety events including: adverse events (AEs), adverse events of special interest (AESIs), and dose limiting toxicities (DLTs) (time frame: Day 1 through Month 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2025.