Clinical trial NCT05643742: A Safety and Efficacy Study Evaluating CTX112 in Subjects With Relapsed or Refractory B-Cell Malignancies
Official title: A Phase 1/2, Open-Label, Multicenter, Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Anti-CD19 Allogeneic CRISPR-Cas9-Engineered T Cells (CTX112) in Subjects With Relapsed or Refractory B Cell Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-cell Lymphoma
Non-Hodgkin Lymphoma
B-cell Malignancy
Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Follicular Lymphoma
Mantle Cell Lymphoma
Marginal Zone Lymphoma
Large B-cell Lymphoma
Keywords: CAR T
Non-Hodgkin Lymphoma (NHL)
Lymphoma
Allogeneic
Lead sponsor: CRISPR Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-12-09
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

Eligibility 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.

Primary outcomes:
measure: Phase 1 (Dose Escalation): Incidence of adverse events, defined as dose-limiting toxicities
timeFrame: From CTX112 infusion up to 28 days post-infusion
measure: Phase 2 (Cohort Expansion): Objective response rate
timeFrame: From CTX112 infusion up to 60 months post-infusion
Secondary outcomes:
measure: Duration of Response
timeFrame: 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
measure: Duration of Clinical Benefit (DOCB)
timeFrame: From date of first objective response of CR/PR until the relapse or death that followed the last response, assessed up to 60 months
measure: Progression Free Survival
timeFrame: From date of CTX112 infusion until date of disease progression or death due to any cause, assessed up to 60 months
measure: Overall Survival
timeFrame: From date of CTX112 infusion until date of death due to any cause, assessed up to 60 months
Other outcomes:
Locations:
city: Westwood
country: United States
facility: Research Site
state: Kansas
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Camperdown
country: Australia
facility: Research Site
state: New South Wales
city: Melbourne
country: Australia
facility: Research Site
state: Victoria
city: Nedlands
country: Australia
facility: Research Site
state: Western Australia
Study officials:
affiliation: CRISPR Therapeutics
name: Annie Weaver, PhD
role: STUDY_DIRECTOR
References: