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

Sponsor

CRISPR Therapeutics AG (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04035434

Collaborator

(none)

143

Enrollment

Locations

Arm

84.3

Anticipated Duration (Months)

5.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, multicenter, Phase 1 study evaluating the safety and efficacy of CTX110 in subjects with relapsed or refractory B-cell malignancies.

Condition or Disease	Intervention/Treatment	Phase
B-cell Malignancy Non-Hodgkin Lymphoma B-cell Lymphoma Adult B Cell ALL	Biological: CTX110	Phase 1

Detailed Description

The study may enroll up to 143 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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

143 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jul 22, 2019

Anticipated Primary Completion Date :

Jul 1, 2026

Anticipated Study Completion Date :

Aug 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CTX110 Administered by IV infusion following lymphodepleting chemotherapy.	Biological: CTX110 CTX110 (CD19-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components

Arm

Intervention/Treatment

Experimental: CTX110

Administered by IV infusion following lymphodepleting chemotherapy.

Biological: CTX110

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

Outcome Measures

Primary Outcome Measures

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]
Part B (Cohort Expansion), for NHL: Objective response rate [From CTX110 infusion up to 60 months post-infusion]

Secondary Outcome Measures

Duration of Response [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
Duration of Clinical Benefit (DOCB) [From date of first objective response of CR/PR until the relapse or death that followed the last response, assessed up to 60 months]
Progression Free Survival [From date of CTX110 infusion until date of disease progression or death due to any cause, assessed up to 60 months]
Overall Survival [From date of 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 [CRi]) will be assessed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

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.
Agree to participate in an additional long-term follow-up study after completion of this study.

Key Exclusion Criteria:

Treatment with any gene therapy or genetically modified cell therapy, including CAR T cells.
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 or requires IV anti-infectives.
Active HIV, 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 enrollment. For B cell ALL patients: Use of systemic antitumor therapy within 7 days of enrollment.
Primary immunodeficiency disorder or active autoimmune disease requiring steroids and/or other immunosuppressive therapy.
Women who are pregnant or breastfeeding.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars Sinai	Los Angeles	California	United States	90048
2	UCSF Medical Center	San Francisco	California	United States	94143
3	Mayo Clinic	Jacksonville	Florida	United States	32224
4	Emory University Winship Cancer Institute	Atlanta	Georgia	United States	30322
5	University of Chicago	Chicago	Illinois	United States	60637
6	University of Kansas	Westwood	Kansas	United States	66205
7	Markey Cancer Center, University of Kentucky	Lexington	Kentucky	United States	40536
8	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
9	University of Minnesota	Minneapolis	Minnesota	United States	55455
10	Washington University	Saint Louis	Missouri	United States	63130
11	Roswell Park Cancer Insitute	Buffalo	New York	United States	14203
12	Weill Cornell Medical College / New York Presbyterian Hospital	New York	New York	United States	10021
13	Oregon Health and Science University	Portland	Oregon	United States	97239
14	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
15	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
16	Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center	Dallas	Texas	United States	75390
17	Texas Transplant Institute	San Antonio	Texas	United States	78229
18	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298
19	Swedish Cancer Institute	Seattle	Washington	United States	98104
20	Royal Prince Alfred Hospital	Sydney	New South Wales	Australia	2050
21	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3000
22	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
23	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
24	University of Hamburg	Hamburg		Germany	20148
25	University Hospital Würzburg	Würzburg		Germany	97080
26	Clinica Universidad de Navarra	Pamplona	Navarra	Spain	31008
27	Hospital Clínic de Barcelona	Barcelona		Spain	08036
28	Hospital Universitario de Salamanca	Salamanca		Spain	37007