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

Non-Hodgkin Lymphoma Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04035434
• Other study ID #: CRSP-ONC-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 22, 2019
• Est. completion date: August 2026

Study information

• Verified date: March 2024
• Source: CRISPR Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 227
• Est. completion date: August 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adult B Cell ALL
• B-cell Lymphoma
• B-cell Malignancy
• Lymphoma
• Lymphoma, Non-Hodgkin
• Neoplasms
• Non-Hodgkin Lymphoma

Intervention

Biological:
• CTX110
CTX110 (CD19-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Royal Prince Alfred Hospital	Sydney	New South Wales
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
France	CHU de Lille	Lille
France	Institut Paoli-Calmettes	Marseille
France	Hôpital Saint Antoine	Paris
Germany	University of Hamburg	Hamburg
Germany	University Hospital Würzburg	Würzburg
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Universitario de Salamanca	Salamanca
United States	Emory University Winship Cancer Institute	Atlanta	Georgia
United States	University of Maryland	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Roswell Park Cancer Insitute	Buffalo	New York
United States	University of Chicago	Chicago	Illinois
United States	Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Mayo Clinic	Jacksonville	Florida
United States	Markey Cancer Center, University of Kentucky	Lexington	Kentucky
United States	Cedars Sinai	Los Angeles	California
United States	University of Minnesota	Minneapolis	Minnesota
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Weill Cornell Medical College / New York Presbyterian Hospital	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Washington University	Saint Louis	Missouri
United States	Texas Transplant Institute	San Antonio	Texas
United States	UCSF Medical Center	San Francisco	California
United States	Swedish Cancer Institute	Seattle	Washington
United States	University of Kansas	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
CRISPR Therapeutics AG

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Phase 1 Part B (Cohort Expansion) and Phase 2: Objective response rate		From CTX110 infusion up to 60 months post-infusion
Secondary	Duration of Response	Duration of Response (DOR) for subjects with objective response events	From date of first objective response until date of disease progression or death due to any cause, assessed up to 60 months
Secondary	Duration of Clinical Benefit (DOCB)		From date of first objective response until date of last disease progression or death, assessed up to 60 months
Secondary	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
Secondary	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
Secondary	Overall Survival (OS)		From date of first CTX110 infusion until date of death due to any cause, assessed up to 60 months
Secondary	Objective Response Rate (for B cell ALL)	For B cell ALL, objective response rate (ORR) (complete remission + complete remission with incomplete blood count recovery) will be assessed.	From CTX110 infusion up to 60 months post-infusion