CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy for Relapsed/Refractory B Cell Non-Hodgkin Lymphoma

• Sponsor: Caribou Biosciences, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04637763
• Collaborator: (none)
• Enrollment: 50
• Locations: 8
• Arms: 2
• Anticipated Duration (Months): 51.2
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

CB010A is a study evaluating safety, emerging efficacy, pharmacokinetics and immunogenicity of CB-010 in adults with relapsed/refractory B cell non-Hodgkin lymphoma after lymphodepletion consisting of cyclophosphamide and fludarabine.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Non-Hodgkin; Relapsed Non Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Non Hodgkin Lymphoma; Lymphoma; B Cell Lymphoma; B Cell Non-Hodgkin's Lymphoma	Genetic: CB-010; Drug: Cyclophosphamide; Drug: Fludarabine	Phase 1

Detailed Description

This clinical trial is a first-in-human, Phase 1, multicenter, open-label evaluation of safety and emerging efficacy of CB-010 in adults with relapsed/refractory B cell non-Hodgkin lymphoma. The study is conducted in two parts: Part A is dose escalation following a 3 + 3 design, with sequential, prespecified, increasing doses. Part B is the expansion portion where patients will receive CB-010 at the dose determined in Part A.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 50 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: The CB10A clinical study consists of 3 + 3 design with three dose levels.The CB10A clinical study consists of 3 + 3 design with three dose levels.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Multicenter, Open-Label Study of CB-010, a CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy in Patients With Relapsed/Refractory B Cell Non-Hodgkin Lymphoma (ANTLER)
• Actual Study Start Date: May 26, 2021
• Anticipated Primary Completion Date: Aug 1, 2025
• Anticipated Study Completion Date: Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation of CB-010 Patients with relapsed or refractory non-Hodgkin lymphoma will receive CB-010 following lymphodepletion.	Genetic: CB-010; CB-010 is a CRISPR-edited allogeneic CAR-T cell therapy targeting CD19.; Drug: Cyclophosphamide; Chemotherapy for lymphodepletion; Drug: Fludarabine; Chemotherapy for lymphodepletion
Experimental: Expansion of CB-010 Patients with relapsed or refractory non-Hodgkin lymphoma will receive CB-010 following lymphodepletion.	Genetic: CB-010; CB-010 is a CRISPR-edited allogeneic CAR-T cell therapy targeting CD19.; Drug: Cyclophosphamide; Chemotherapy for lymphodepletion; Drug: Fludarabine; Chemotherapy for lymphodepletion

Outcome Measures

Primary Outcome Measures

1. Primary outcome measures number of patients with dose-limiting toxicities (Part A). [28 days following CB-010 infusion]

   Incidence of adverse events defined as dose-limiting toxicities with onset within 28 days after CB-010 infusion.

2. Primary outcome evaluates tumor response (Part B) [Up to 12 months]

   The primary endpoint is objective response rate.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age greater than or equal to 18 at the time of enrollment

• Documented diagnosis of relapsed or refractory non-Hodgkin lymphoma after prior standard of care

• Eastern Cooperative Oncology Group performance status 0 or 1

• Adequate hematologic, renal, liver, cardiac and pulmonary organ function

Exclusion Criteria:

• Prior therapy with an anti-CD19 targeting agent

• Active or chronic graft versus host disease requiring therapy

• Prior allogeneic stem cell transplantation

• Central nervous system (CNS) lymphoma, prior CNS malignancy

• Prior seizure disorder, cerebrovascular ischemia, dementia, cerebellar disease or autoimmune disease with CNS involvement.

• Primary immunodeficiency

• Current or expected need for systemic corticosteroid therapy

• Current thyroid disorder. Hypothyroidism controlled with stable hormone replacement is permitted

• Other malignancy within 2 years of study entry, except curatively treated malignancies or malignancies with low risk of recurrence

• Unwillingness to follow extended safety monitoring

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HonorHealth	Scottsdale	Arizona	United States	85258
2	University of California San Diego Moores Cancer Center	La Jolla	California	United States	92073
3	Chao Family Comprehensive Cancer Center/University of California Irvine	Orange	California	United States	92868
4	Oncology Hematology Care	Cincinnati	Ohio	United States	45242
5	Ohio State University James Cancer Hospital	Columbus	Ohio	United States	43210
6	Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
7	MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
8	Huntsman Cancer Institute at the University of Utah	Salt Lake City	Utah	United States	84112

Sponsors and Collaborators

• Caribou Biosciences, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Caribou Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT04637763
• Other Study ID Numbers: CB10A
• First Posted: Nov 20, 2020
• Last Update Posted: Aug 22, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Cyclophosphamide; Fludarabine

Study Results

No Results Posted as of Aug 22, 2022