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).

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
• Results First Submitted: 2025-07-08
• Status Verified: 2025-10
• Results First Submitted QC: 2025-10-09
• Last Update Submitted: 2025-10-09
• Results First Posted: 2025-10-24
• Last Update Posted: 2025-10-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 93

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 & 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
Dose Escalation Phase 1: Number of Participants With Dose-limiting Toxicities (DLT) in NHL and B Cell ALL Population	Up to 28 days	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.
Dose Expansion Phase 1 and Phase 2: Percentage of Participants With Objective Response Rate in NHL Population	Up to 5 years	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.

Secondary Outcome Measures

Name	Time	Method
Dose Escalation Phase 1: Percentage of Participants With Objective Response Rate in B Cell ALL Population	Up to 5 years	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.
Dose Escalation and Expansion Phase 1: Duration of Response in NHL Population	Up to 5 years	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.
Dose Escalation and Expansion Phase 1: Progression Free Survival (PFS) in NHL Population	Up to 5 years	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.
Dose Escalation and Expansion Phase 1: Median Overall Survival (OS) in NHL Population	Up to 5 years	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.
Dose Escalation and Expansion: Number of Participants With Treatment Emergent Adverse Events (TEAEs) in NHL and B Cell ALL Population	Up to 5 years	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.
Dose Escalation and Expansion: Number of Participants With Clinically Significant Laboratory Abnormalities in NHL and B Cell ALL Population	Up to 5 years	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.
Dose Escalation and Expansion: Mean Concentration of CTX110 in Blood Over Time Following the First CTX110 Infusion in NHL Population	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	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.
Dose Escalation and Expansion Phase 1: Mean Concentration of CTX110 in Blood Over Time Following the First CTX110 Infusion in B Cell ALL Population	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	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.
Dose Escalation and Expansion: Number of Participants With Serious Adverse Events (SAEs) in NHL and B Cell ALL Population	Up to 5 years	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.

Trial Locations

Locations (33)

Cedars Sinai; 🇺🇸 Los Angeles, California, United States

UCSF Medical Center; 🇺🇸 San Francisco, California, United States

Mayo Clinic; 🇺🇸 Jacksonville, Florida, United States

Emory University Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

University of Kansas; 🇺🇸 Westwood, Kansas, United States

Markey Cancer Center, University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

University of Maryland; 🇺🇸 Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

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