A Study of bbT369 in Relapsed and/or Refractory B Cell Non-Hodgkin's Lymphoma (NHL)

Diffuse Large B Cell Lymphoma (DLBCL) Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05169489
• Other study ID #: CRC-403
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 24, 2022
• Est. completion date: August 2025

Study information

• Verified date: March 2024
• Source: 2seventy bio
• Contact: Clinical Trials Office
• Phone: 617-798-4270
• Email: clinicaltrials[@]2seventybio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: August 2025
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma (DLBCL)
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin

Intervention

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.

Locations

Country	Name	City	State
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Sarah Cannon	Nashville	Tennessee
United States	Stanford Cancer Institute	Stanford	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
2seventy bio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Phase 1: Overall Response Rate (ORR) according to the Lugano 2014 response criteria as assessed by Investigator		Day 1 through Month 24
Secondary	Phase 1: Time to response (TTR)		Day 1 through Month 24
Secondary	Phase 1: Time to complete response (TCR)		Day 1 through Month 24
Secondary	Phase 1: Time to next treatment for B Cell NHL (TTNT)		Day 1 through Month 24