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

Sponsor
2seventy bio (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05169489
Collaborator
(none)
50
2
1
42.2
25
0.6

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
  • Biological: bbT369
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

Study Type:
Interventional
Anticipated Enrollment :
50 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Jan 24, 2022
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Aug 1, 2025

Arms and Interventions

Arm Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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]

  2. Phase 1: Overall Response Rate (ORR) according to the Lugano 2014 response criteria as assessed by Investigator [Day 1 through Month 24]

  3. Phase 1: Time to response (TTR) [Day 1 through Month 24]

  4. Phase 1: Time to complete response (TCR) [Day 1 through Month 24]

  5. Phase 1: Time to next treatment for B Cell NHL (TTNT) [Day 1 through Month 24]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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.

Contacts and Locations

Locations

Site City State Country Postal Code
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.
Responsible Party:
2seventy bio
ClinicalTrials.gov Identifier:
NCT05169489
Other Study ID Numbers:
  • CRC-403
First Posted:
Dec 27, 2021
Last Update Posted:
Feb 28, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by 2seventy bio
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 28, 2022