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

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)

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.

Study Overview

• Status: Terminated
• Conditions: B-cell Lymphoma; Non-Hodgkin Lymphoma; B-cell Malignancy; Adult B Cell ALL
• Intervention / Treatment: Biological: CTX110

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).

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
• France
  • Lille, France, 59000
    • CHU de Lille
  • Marseille, France, 13009
    • Institut Paoli-Calmettes
  • Paris, France, 75012
    • Hopital Saint Antoine
• Germany
  • Hamburg, Germany, 20148
    • University of Hamburg
  • Würzburg, Germany, 97080
    • University Hospital Wurzburg
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai
    • San Francisco, California, United States, 94143
      • UCSF Medical Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Markey Cancer Center, University of Kentucky
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • St Louis, Missouri, United States, 63130
      • Washington University
  • New York
    • Buffalo, New York, United States, 14203
      • Roswell Park Cancer Insitute
    • New York, New York, United States, 10021
      • Weill Cornell Medical College / New York Presbyterian Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75390
      • Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center
    • San Antonio, Texas, United States, 78229
      • Texas Transplant Institute
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Massey Cancer Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation Phase 1: Number of Participants With Dose-limiting Toxicities (DLT) in NHL and B Cell ALL Population	A DLT is defined as any of the following events occurring during the DLT evaluation period that persisted beyond the specified duration from onset: Grade ≥2 graft-versus-host disease (GvHD) that was steroid-refractory (e.g., progressive disease after 3 days of steroid treatment [e.g., 1 mg/kg/day], stable disease after 7 days, or partial response after 14 days of treatment); death during the DLT period, unless due to disease progression; Grade 4 neurotoxicity of any duration that was related or possibly related to CTX110; or any CTX110-related grade 3 or 4 toxicity deemed clinically significant by the investigator that did not improve within 72 hours.	Up to 28 days
Dose Expansion Phase 1 and Phase 2: Percentage of Participants With Objective Response Rate in NHL Population	The objective response rate (complete response + partial response) was analyzed as per Lugano Response Criteria for Malignant Lymphoma, as determined by independent central radiology review. For participants who received the second course of treatment, the response assessments before and after the second course are combined for the derivation of objective response. Percentages are calculated with the number of participants in the specific analysis set in each column as the denominator. Confidence intervals (CI) of percentage are calculated with Clopper-Pearson exact method.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation Phase 1: Percentage of Participants With Objective Response Rate in B Cell ALL Population	The objective response rate (complete response + complete remission with incomplete blood count recovery) was analyzed as per response criteria adapted from the National Comprehensive Cancer Network guidelines for treatment of acute lymphoblastic leukemia Version 2.2021, as determined by independent central radiology review. For -participants who receive the second course of treatment, the response assessments before and after the second course are combined for the derivation of objective response. Percentages are calculated with the number of participants in the specific analysis set in each column as the denominator. Confidence intervals (CI) of percentage are calculated with Clopper-Pearson exact method.	Up to 5 years
Dose Escalation and Expansion Phase 1: Duration of Response in NHL Population	Duration of response was only reported for the participants who showed objective response events. This was calculated as the time between first objective response and date of disease progression or death due to any cause. Median duration of response was calculated with the Kaplan-Meier method. Confidence intervals of median duration of response were calculated with the Brookmeyer and Crowley method with log-log transformation.	Up to 5 years
Dose Escalation and Expansion Phase 1: Progression Free Survival (PFS) in NHL Population	Progression-free survival (PFS) and event-free survival were calculated as the difference between date of CTX110 infusion and date of disease progression or death due to any cause. The median of PFS was calculated with the Kaplan-Meier method. The CIs of median PFS were calculated with the Brookmeyer and Crowley method with log-log transformation.	Up to 5 years
Dose Escalation and Expansion Phase 1: Median Overall Survival (OS) in NHL Population	Overall survival was calculated as the time between date of first dose of CTX110 and death due to any cause. Participants who are alive at the data cutoff date will be censored at their last date known to be alive. Median overall survival was calculated with the Kaplan-Meier method. CIs of median overall survival were calculated with the Brookmeyer and Crowley method with log-log transformation.	Up to 5 years
Dose Escalation and Expansion: Number of Participants With Treatment Emergent Adverse Events (TEAEs) in NHL and B Cell ALL Population	A TEAE was any untoward medical occurrence or worsening of a pre-existing condition in a clinical trial participant who received the investigational medicinal product, regardless of a causal relationship with the treatment. An AE had to be classified as a serious adverse event (SAE) if it resulted in death, was life-threatening, required or prolonged hospitalization, caused persistent or significant disability or incapacity, led to a congenital anomaly or birth defect in a newborn, or was deemed a significant medical event by the investigator based on medical judgment.	Up to 5 years
Dose Escalation and Expansion: Number of Participants With Clinically Significant Laboratory Abnormalities in NHL and B Cell ALL Population	Blood samples were collected for the analysis of laboratory parameters including hematology, clinical chemistry and coagulation parameters. The hematology parameters included: Lymphocyte count decreased, Neutrophil count decreased, White blood cell decreased, Anemia, Platelet count decreased, leukocytosis and Lymphocyte count increased. Chemistry parameters included: Hypoalbuminemia, Aspartate aminotransferase increased, Alanine aminotransferase increased, Hypokalemia, Chronic kidney disease, Blood bilirubin increased, Creatinine increased, Hypermagnesemia, Hypernatremia, Hypercalcemia, Hyperkalemia, and Hypoglycemia. Coagulation parameters included: Activated partial thromboplastin time prolonged, Fibrinogen decreased, and INR increased. Grade 3 and above severity of laboratory abnormalities are considered as clinically significant laboratory abnormalities.	Up to 5 years
Dose Escalation and Expansion: Mean Concentration of CTX110 in Blood Over Time Following the First CTX110 Infusion in NHL Population	Blood samples were collected for the analysis of mean concentration of CTX110 in blood (copies per micrograms deoxyribose nucleic acid [DNA]) over time following the first CTX110 infusion. Cohort A DL4a and DL4b were combined, as the same dose was administered. Mean concentration values of CTX110 have been presented by dose level.	Day 1 pre-infusion, Day 1 post-infusion, Day 2, Day 3, Day 5, Day 8, Day 10, Day 14, Day 21, Day 28, Month 2, Month 3, Month 6, Month 9, Month 12 and Month 24
Dose Escalation and Expansion Phase 1: Mean Concentration of CTX110 in Blood Over Time Following the First CTX110 Infusion in B Cell ALL Population	Blood samples were collected for the analysis of mean concentration of CTX110 in blood (copies per micrograms deoxyribose nucleic acid [DNA]) over time following the first CTX110 infusion.	Day 1 pre-infusion, Day 1 post-infusion, Day 2, Day 3, Day 5, Day 8, Day 10, Day 14, Day 21, Day 28, and Month 2
Dose Escalation and Expansion: Number of Participants With Serious Adverse Events (SAEs) in NHL and B Cell ALL Population	An AE had to be classified as a serious adverse event (SAE) if it resulted in death, was life-threatening, required or prolonged hospitalization, caused persistent or significant disability or incapacity, led to a congenital anomaly or birth defect in a newborn, or was deemed a significant medical event by the investigator based on medical judgment.	Up to 5 years

Collaborators and Investigators

• Sponsor: CRISPR Therapeutics AG
• Investigators: Study Director: Annie Weaver, PhD, CRISPR Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2019
• Primary Completion (Actual): October 4, 2024
• Study Completion (Actual): October 4, 2024

Study Registration Dates

• First Submitted: July 22, 2019
• First Submitted That Met QC Criteria: July 25, 2019
• First Posted (Actual): July 29, 2019

Study Record Updates

• Last Update Posted (Estimated): October 24, 2025
• Last Update Submitted That Met QC Criteria: October 9, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Lymphoma; NHL; Leukemia; Allogeneic; Non-Hodgkin Lymphoma; CAR T
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Infections; Virus Diseases; Neoplasms by Histologic Type; Hematologic Diseases; DNA Virus Infections; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Epstein-Barr Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Hemic and Lymphatic Diseases; Leukemia; Lymphoma; Lymphoma, B-Cell; Burkitt Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: CRSP-ONC-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No