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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
93
CTX110 (CD19-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components
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.
Time frame: 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.
Time frame: Up to 5 years
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.
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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
...and 23 more locations
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 5 years