A Safety and Efficacy Study Evaluating CTX110 in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON)

Study Overview
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Brief Summary
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This is an open-label, multicenter, Phase 1/2 study evaluating the safety and efficacy of CTX110 in subjects with relapsed or refractory B-cell malignancies.

Detailed Description
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The study may enroll up to 227 subjects in total. CTX110 is a CD19-directed chimeric antigen receptor (CAR) T cell immunotherapy comprised of allogeneic T cells prepared for the treatment of B cell malignancies. The cells are from healthy adult volunteer donors that are genetically modified ex vivo using CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/ CRISPR-associated protein 9) gene editing components (single guide RNA and Cas9 nuclease).

Official Title
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A Phase 1/2 Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Allogeneic CRISPR-Cas9-Engineered T Cells (CTX110) in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON)

Conditions
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B-cell Malignancy, Non-Hodgkin Lymphoma, B-cell Lymphoma, Adult B Cell ALL

Intervention / Treatment
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* Biological: CTX110


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: For NHL patients: Age ≥18 years. For B cell ALL patients: age ≥18 years to ≤70 years Refractory or relapsed non-Hodgkin lymphoma, as evidenced by 2 or more lines of prior therapy, or histologically confirmed B cell ALL, refractory or relapsed. Eastern Cooperative Oncology Group performance status 0 or 1. Adequate renal, liver, cardiac and pulmonary organ function Female subjects of childbearing potential and male subjects must agree to use acceptable method(s) of contraception from enrollment through at least 12 months after CTX110 infusion. Key Exclusion Criteria: For NHL patients: prior allogeneic HSCT. For B cell ALL patients: prior allogeneic HSCT within 6 months, and/or any evidence of GvHD. History of central nervous system (CNS) involvement by malignancy History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement. Presence of bacterial, viral, or fungal infection that is uncontrolled. Positive for HIV, or active hepatitis B virus or hepatitis C virus infection. Previous or concurrent malignancy, except basal cell or squamous cell skin carcinoma, adequately resected and in situ carcinoma of cervix, or a previous malignancy that was completely resected and has been in remission for ≥5 years. For NHL patients: Use of systemic anti-tumor therapy or investigational agent within 14 days or 5 half-lives, whichever is longer, of CTX110 infusion. For B cell ALL patients: Use of systemic antitumor therapy within 7 days of CTX110 infusion. Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy. Women who are pregnant or breastfeeding.

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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CTX110<br>Administered by IV infusion following lymphodepleting chemotherapy. | Biological: CTX110<br>* CTX110 (CD19-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 Part A (Dose Escalation), for all cohorts: Incidence of adverse events, defined as dose-limiting toxicities |  | From CTX110 infusion up to 28 days post-infusion | 
| Phase 1 Part B (Cohort Expansion) and Phase 2: Objective response rate |  | From CTX110 infusion up to 60 months post-infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | Duration of Response (DOR) for subjects with objective response events | From date of first objective response until date of disease progression or death due to any cause, assessed up to 60 months | 
| Duration of Clinical Benefit (DOCB) |  | From date of first objective response until date of last disease progression or death, assessed up to 60 months | 
| Treatment-Failure-Free Survival (TFFS) |  | From date of first CTX110 infusion until date of last disease progression or death due to any cause, assessed up to 60 months | 
| Progression Free Survival (PFS) |  | From date of first CTX110 infusion until date of first disease progression or death due to any cause, assessed up to 60 months | 
| Overall Survival (OS) |  | From date of first CTX110 infusion until date of death due to any cause, assessed up to 60 months | 
| Objective Response Rate (for B cell ALL) | For B cell ALL, objective response rate (ORR) (complete remission + complete remission with incomplete blood count recovery) will be assessed. | From CTX110 infusion up to 60 months post-infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR T, Non-Hodgkin Lymphoma, NHL, Lymphoma, Allogeneic, Leukemia