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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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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

Intervention / Treatment
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* Genetic: CB-010
* Drug: Cyclophosphamide
* Drug: Fludarabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: The CB10A clinical study consists of (Part A) 3 + 3 design with three dose levels. (Part B) Expansion portion patients will receive CB-010 at the dose determined in Part A.
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary outcome measures number of patients with dose-limiting toxicities (Part A). | Incidence of adverse events defined as dose-limiting toxicities with onset within 28 days after CB-010 infusion. | 28 days following CB-010 infusion | 
| Primary outcome evaluates tumor response (Part B) | The primary endpoint is objective response rate. | Up to 12 months |