A Safety and Efficacy Study Evaluating CTX110 in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON)
- Conditions
- Non-Hodgkin LymphomaB-cell LymphomaAdult B Cell ALLB-cell Malignancy
- Interventions
- Registration Number
- NCT04035434
- Lead Sponsor
- CRISPR Therapeutics AG
- 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).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 62
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description CTX110 CTX110 Administered by IV infusion following lymphodepleting chemotherapy.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 Duration of Response From date of first objective response until date of disease progression or death due to any cause, assessed up to 60 months Duration of Response (DOR) for subjects with objective response events
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 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) From CTX110 infusion up to 60 months post-infusion For B cell ALL, objective response rate (ORR) (complete remission + complete remission with incomplete blood count recovery) will be assessed.
Trial Locations
- Locations (33)
University of Maryland
🇺🇸Baltimore, Maryland, United States
Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Royal Prince Alfred Hospital
🇦🇺Sydney, New South Wales, Australia
Emory University Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
University of Hamburg
🇩🇪Hamburg, Germany
Mayo Clinic
🇺🇸Jacksonville, Florida, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Weill Cornell Medical College / New York Presbyterian Hospital
🇺🇸New York, New York, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Roswell Park Cancer Insitute
🇺🇸Buffalo, New York, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Cedars Sinai
🇺🇸Los Angeles, California, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
University of Kansas
🇺🇸Westwood, Kansas, United States
Markey Cancer Center, University of Kentucky
🇺🇸Lexington, Kentucky, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Duke University
🇺🇸Durham, North Carolina, United States
Texas Transplant Institute
🇺🇸San Antonio, Texas, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
CHU de Lille
🇫🇷Lille, France
Hôpital Saint Antoine
🇫🇷Paris, France
University Hospital Würzburg
🇩🇪Würzburg, Germany
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Clínic de Barcelona
🇪🇸Barcelona, Spain
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Institut Paoli-Calmettes
🇫🇷Marseille, France
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain