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

Primary Purpose

Diffuse Large B Cell Lymphoma (DLBCL)

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

bbT369

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma (DLBCL) focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Stanford Cancer InstituteRecruiting
Colorado Blood Cancer InstituteRecruiting
Moffitt Cancer CenterRecruiting
Sarah CannonRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

bbT369 Experimental Arm

Arm Description

Open label, single arm treatment with bbT369

Outcomes

Primary Outcome Measures

Phase 1: Incidence of safety events including: adverse events (AEs), adverse events of special interest (AESIs), and dose limiting toxicities (DLTs)

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

Phase 1: Overall Response Rate (ORR) according to the Lugano 2014 response criteria as assessed by Investigator

Phase 1: Time to response (TTR)

Phase 1: Time to complete response (TCR)

Phase 1: Time to next treatment for B Cell NHL (TTNT)

Full Information

NCT ID

NCT05169489

First Posted

December 11, 2021

Last Updated

July 5, 2023

Sponsor

2seventy bio

1. Study Identification

Unique Protocol Identification Number

NCT05169489

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 24, 2022 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

August 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

2seventy bio

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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), 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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

bbT369 Experimental Arm

Arm Type

Experimental

Arm Description

Open label, single arm treatment with bbT369

Intervention Type

Biological

Intervention Name(s)

bbT369

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Time Frame

Day 1 through Month 24

Title

Phase 1: Overall Response Rate (ORR) according to the Lugano 2014 response criteria as assessed by Investigator

Time Frame

Day 1 through Month 24

Title

Phase 1: Time to response (TTR)

Time Frame

Day 1 through Month 24

Title

Phase 1: Time to complete response (TCR)

Time Frame

Day 1 through Month 24

Title

Phase 1: Time to next treatment for B Cell NHL (TTNT)

Time Frame

Day 1 through Month 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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: 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 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. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Clinical Trials Office

Phone

617-798-4270

clinicaltrials@2seventybio.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anna Truppel-Hartmann, MD

Organizational Affiliation

2seventy bio, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Stanford Cancer Institute

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David Miklos, MD, PhD

Phone

650-452-8155

dmiklos@stanford.edu

Facility Name

Colorado Blood Cancer Institute

City

Denver

State/Province

Colorado

ZIP/Postal Code

80218

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michael Tees, MD

Phone

720-754-4800

Facility Name

Moffitt Cancer Center

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marissa Folsom

Marissa.Folsom@moffitt.org

Facility Name

Sarah Cannon

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ian Flinn, MD

Phone

615-329-7274

12. IPD Sharing Statement

Plan to Share IPD

Yes

Learn more about this trial

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

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