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

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.

• CB-010 (Genetic): CB-010 is a CRISPR-edited allogeneic CAR-T cell therapy targeting CD19.
• Cyclophosphamide (Drug): Chemotherapy for lymphodepletion
• Fludarabine (Drug): Chemotherapy for lymphodepletion

Primary outcomes

• 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.
• Primary outcome evaluates tumor response (Part B) [Up to 12 months]: The primary endpoint is objective response rate.

Sex: All, ages: 18 Years to any

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