B-cell Lymphoma, B-cell Malignancy, Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), Follicular Lymphoma, Large B-cell Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Non-Hodgkin Lymphoma
Conditions
Keywords
CAR T, Non-Hodgkin Lymphoma (NHL), Lymphoma, Allogeneic
Brief summary
This is an open-label, multicenter, Phase 1/2 study evaluating the safety and efficacy of CTX112™ in subjects with relapsed or refractory B-cell malignancies.
Detailed description
This is an open-label, multi-center Phase 1/2 study of CTX112 in subjects with relapsed/refractory B cell malignancies. CTX112 is an is allogeneic CD19-directed chimeric antigen receptor (CAR) T cell immunotherapy comprised of allogeneic T cells 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).
Interventions
BIOLOGICALCTX112
CTX112 (CD19-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components)
Sponsors
CRISPR Therapeutics AG
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Age ≥18 years. 2. Refractory or relapsed B cell malignancy. 3. Eastern Cooperative Oncology Group performance status 0 or 1. 4. Adequate renal, liver, cardiac and pulmonary organ function. 5. 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 CTX112 infusion. Key
Exclusion criteria
1. Prior allogeneic hematopoietic stem cell transplant (HSCT). 2. Active or history of central nervous system (CNS) involvement by malignancy. 3. History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement. 4. Presence of bacterial, viral, or fungal infection that is uncontrolled or requires IV anti-infectives. 5. Active HIV, hepatitis B virus or hepatitis C virus infection. 6. Previous or concurrent malignancy in the last 3 years (with the exception of non-melanoma skin cancer and other cancers deemed by the investigator and medical monitor to be of low likelihood for recurrence). 7. Concurrent systemic treatment with an anticancer biologic (e.g., monoclonal antibody) within 30 days prior to CTX112 infusion or with a nonbiological anticancer drug within 14 days prior to CTX112 infusion. 8. Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy. 9. Women who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1 (Dose Escalation): Incidence of adverse events, defined as dose-limiting toxicities | From CTX112 infusion up to 28 days post-infusion |
| Phase 2 (Cohort Expansion): Objective response rate | From CTX112 infusion up to 60 months post-infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | From date of first objective response of complete response (CR)/partial response (PR) until date of disease progression or death due to any cause, assessed up to 60 months | Duration of Response (DOR) will only be reported for subjects who have had CR/PR events |
| Duration of Clinical Benefit (DOCB) | From date of first objective response of CR/PR until the relapse or death that followed the last response, assessed up to 60 months | — |
| Progression Free Survival | From date of CTX112 infusion until date of disease progression or death due to any cause, assessed up to 60 months | — |
| Overall Survival | From date of CTX112 infusion until date of death due to any cause, assessed up to 60 months | — |
Countries
Australia, United States
Contacts
Primary ContactClinical Trials
Outcome results
None listed