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

Phase 1

Terminated

• Conditions: Non-Hodgkin Lymphoma; B-cell Lymphoma; Adult B Cell ALL; B-cell Malignancy
• Interventions: Biological: CTX110

• 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).

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2019-07-22
• Study First Submitted: 2019-07-22
• Study First Submitted QC: 2019-07-25
• Study First Posted: 2019-07-29
• Primary Completion: 2024-10-04
• Study Completion: 2024-10-04
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-07
• Last Update Posted: 2025-01-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 62

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

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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.

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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