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

• ClinicalTrials.gov Identifier: NCT04035434
• Recruitment Status: Recruiting
• First Posted: July 29, 2019
• Last Update Posted: January 8, 2021
• Sponsor: CRISPR Therapeutics AG
• Information provided by (Responsible Party): CRISPR Therapeutics ( CRISPR Therapeutics AG )

Tracking Information

• First Submitted Date: July 22, 2019
• First Posted Date: July 29, 2019
• Last Update Posted Date: January 8, 2021
• Actual Study Start Date: July 22, 2019
• Estimated Primary Completion Date: July 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 1, 2020)

• Part A (Dose Escalation): Incidence of adverse events, defined as dose-limiting toxicities [ Time Frame: From CTX110 infusion up to 28 days post-infusion ]
• Part B (Cohort Expansion): Objective response rate [ Time Frame: From CTX110 infusion up to 60 months post-infusion ]

Original Primary Outcome Measures (submitted: July 25, 2019)

• Phase 1 (Dose Escalation): Incidence of adverse events, defined as dose-limiting toxicities [ Time Frame: From CTX110 infusion up to 28 days post-infusion ]
• Phase 2 (Cohort Expansion): Objective response rate [ Time Frame: From CTX110 infusion up to 60 months post-infusion ]

Current Secondary Outcome Measures (submitted: July 25, 2019)

• Duration of Response [ Time Frame: From date of first objective response of CR/PR until date of disease progression or death due to any cause, assessed up to 60 months ]
  Duration of Response (DOR) will only be reported for subjects who have had CR/PR events
• Progression Free Survival [ Time Frame: From date of CTX110 infusion until date of disease progression or death due to any cause, assessed up to 60 months ]
• Overall Survival [ Time Frame: From date of CTX110 infusion until date of death due to any cause, assessed up to 60 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Safety and Efficacy Study Evaluating CTX110 in Subjects With Relapsed or Refractory B-Cell Malignancies (CARBON)
• Official Title: A Phase 1 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)
• Brief Summary: This is a single-arm, open-label, multicenter, Phase 1 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 131 subjects in total.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• B-cell Malignancy
• Non-Hodgkin Lymphoma
• B-cell 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

Study Arms

Experimental: CTX110

Administered by IV infusion following lymphodepleting chemotherapy.

Intervention: Biological: CTX110

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 20, 2020): 131
• Original Estimated Enrollment (submitted: July 25, 2019): 95
• Estimated Study Completion Date: August 2026
• Estimated Primary Completion Date: July 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. Age ≥18 years.
2. Refractory or relapsed non-Hodgkin lymphoma, as evidenced by 2 or more lines of prior therapy.
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.
6. Agree to participate in an additional long-term follow-up study after completion of this study.

Key Exclusion Criteria:

1. Treatment with any gene therapy or genetically modified cell therapy, including CAR T cells.
2. Prior allogeneic HSCT.
3. History of central nervous system (CNS) involvement by malignancy
4. History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
5. Presence of bacterial, viral, or fungal infection that is uncontrolled or requires IV anti-infectives.
6. Active HIV, hepatitis B virus or hepatitis C virus infection.
7. 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.
8. Use of systemic anti-tumor therapy or investigational agent within 14 days or 5 half-lives, whichever is longer, of enrollment.
9. Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy.
10. Women who are pregnant or breastfeeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trials; +1 (877) 214-4634; MedicalAffairs@crisprtx.com

• Listed Location Countries: Australia, Germany, United States

Administrative Information

• NCT Number: NCT04035434
• Other Study ID Numbers: CRSP-ONC-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: CRISPR Therapeutics ( CRISPR Therapeutics AG )
• Study Sponsor: CRISPR Therapeutics AG
• Collaborators: Not Provided

Investigators

• Study Director: Ewelina Morawa, MD; CRISPR Therapeutics

• PRS Account: CRISPR Therapeutics
• Verification Date: January 2021