Clinical trial NCT04035434: A Safety and Efficacy Study Evaluating CTX110 in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: B-cell Malignancy
Non-Hodgkin Lymphoma
B-cell Lymphoma
Adult B Cell ALL
Keywords: CAR T
Non-Hodgkin Lymphoma
NHL
Lymphoma
Allogeneic
Leukemia
Lead sponsor: CRISPR Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-07-29
Enrollment: 62
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 CTX110 in subjects with relapsed or refractory B-cell malignancies.

Detailed description: 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).

Eligibility criteria: Key Inclusion Criteria:

1. For NHL patients: Age ≥18 years. For B cell ALL patients: age ≥18 years to ≤70 years
2. 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.
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 CTX110 infusion.

Key Exclusion Criteria:

1. For NHL patients: prior allogeneic HSCT. For B cell ALL patients: prior allogeneic HSCT within 6 months, and/or any evidence of GvHD.
2. 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.
5. Positive for HIV, or active hepatitis B virus or hepatitis C virus infection.
6. 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.
7. 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.
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 Part A (Dose Escalation), for all cohorts: Incidence of adverse events, defined as dose-limiting toxicities
timeFrame: From CTX110 infusion up to 28 days post-infusion
measure: Phase 1 Part B (Cohort Expansion) and Phase 2: Objective response rate
timeFrame: From CTX110 infusion up to 60 months post-infusion
Secondary outcomes:
measure: Duration of Response
timeFrame: From date of first objective response 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 until date of last disease progression or death, assessed up to 60 months
measure: Treatment-Failure-Free Survival (TFFS)
timeFrame: From date of first CTX110 infusion until date of last disease progression or death due to any cause, assessed up to 60 months
measure: Progression Free Survival (PFS)
timeFrame: From date of first CTX110 infusion until date of first disease progression or death due to any cause, assessed up to 60 months
measure: Overall Survival (OS)
timeFrame: From date of first CTX110 infusion until date of death due to any cause, assessed up to 60 months
measure: Objective Response Rate (for B cell ALL)
timeFrame: From CTX110 infusion up to 60 months post-infusion
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Westwood
country: United States
facility: University of Kansas
state: Kansas
city: Lexington
country: United States
facility: Markey Cancer Center, University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Insitute
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College / New York Presbyterian Hospital
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Lille
country: France
facility: CHU de Lille
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Hamburg
country: Germany
facility: University of Hamburg
city: Würzburg
country: Germany
facility: University Hospital Würzburg
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
Study officials:
affiliation: CRISPR Therapeutics
name: Annie Weaver, PhD
role: STUDY_DIRECTOR
References: