This is a multi-center, phase Ib/II trial to evaluate the safety and efficacy of CNCT19 treatment in Children and Adolescent (pediatric) patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-cell ALL).
This trial is a multi-center, open label, single-arm, phase Ib/II trial to evaluate the safety and efficacy of CNCT19 in Children and Adolescent(aged 3\~18 years old) patients (pediatric) with r/r B-cell ALL. The phase Ib part of the trial is to evaluate the safety, optimal dose of CNCT19, Pharmacokinetics/Pharmacodynamics(PK/PD)and preliminary efficacy in the treatment of Children and Adolescent patients with r/r B-cell ALL. The phase II part of the trial is to evaluate the efficacy and safety of CNCT19 in in the treatment of Children and Adolescent patients with r/r B-cell ALL. The study includes screening, pre-treatment (Cell Product manufacture \& lymphodepletion), CNCT19 infusion , safety and efficacy follow-up, and survival follow-up. All subjects who have received CNCT19 infusion will be followed for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
47
Autologous 2nd generation CD19-directed CAR-T cells, single infusion intravenously. Lymphodepletion treatment: Drugs:Fludarabine Drugs: Cyclophosphamide
The Second Hospital of Anhui Medical University
Hefei, Anhui, China
NOT_YET_RECRUITINGChildren's Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, China
RECRUITINGOverall Remission Rate (ORR)
ORR is defined as Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) per NCCN classification, as determined by Independent Review Committee (IRC)
Time frame: within 3 months
Overall complete Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators
MRD negativity status as determined using flow cytometry
Time frame: within 3 months
Overall Remission Rate (ORR) as determined by IRC and Investigators
The Investigators' evaluation results of ORR will be utilized in the sensitivity analysis
Time frame: at the end of month 3
Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators
MRD negativity as determined using flow cytometry
Time frame: at the end of Month 3
Best overall response (BOR)
The proportion of patients who have achieved the best response (CR or CRi) after CNCT19 treatment
Time frame: up to 2 years
Duration of remission (DOR)
DOR is defined as the time between their first complete response per independent review to relapse or any death in the absence of documented relapse
Time frame: to data cutoff date
Allogeneic Stem Cell Transplant (Allo-SCT) rate
The proportion of patients who have received Allo-SCT after CNCT19 treatment
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Guangzhou Women and Children's Medical Center
Guangzhou, Guangdong, China
RECRUITINGNanfang Hospital
Guangzhou, Guangdong, China
NOT_YET_RECRUITINGUnion Hospital Tongji Medical College Huazhong University of Science of Technology
Wuhan, Hubei, China
NOT_YET_RECRUITINGChildren's Hospital of Nanjing Medical University
Nanjing, Jiangsu, China
RECRUITINGThe Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, China
RECRUITINGThe First Affilicated Hospital of Nanchang University
Nanchang, Jiangxi, China
RECRUITINGInstitute of Hematology & Blood Diseases Hospital
Tianjin, Tianjin Municipality, China
RECRUITINGTime frame: First infusion date of CNCT19 to data cutoff date(up to 2 years)
Relapse Free Survival (RFS)
RFS is defined as the time from the CNCT19 infusion date to the date of disease relapse or death from any cause.
Time frame: 2 years
Overall survival (OS)
OS is defined as the time from the CNCT19 Cell Injection infusion to the date of death from any cause
Time frame: 2 years
Treatment-Emergent Adverse Events
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE) and Severity of TEAE
Time frame: up to 2 years
Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities
Clinically significant laboratory abnormalities were defined as per investigator's discretion
Time frame: From CNCT19 infusion to date of data cutoff (maximum: 2 years)
In vivo cellular Pharmacokinetic (PK) profile of CNCT19
To characterize the concentration of CAR-T cell in peripheral blood, bone marrow and cerebral spinal fluid (CSF, if available)by Flow Cytometry and quantitative polymerase chain reaction(qPCR).
Time frame: Up to 3 months(BM sample); Up to 2 years(Blood sample)
Pharmacokinetic (PK)- Cmax of CNCT19
Maximum detected concentration of CNCT19 in peripheral blood
Time frame: Up to 2 years
Pharmacokinetic (PK)- Tmax of CNCT19.
Time to maximum concentration of CNCT19 in peripheral blood
Time frame: Up to 2 years
Pharmacokinetic (PK)- AUC of CNCT19.
Area under the concentration (AUC) vs time curve of CNCT19 in peripheral blood
Time frame: Up to 2 years
Concentration of Cytokines in Serum
Collected as pharmacodynamic data, including IL-6 at least
Time frame: 28 days
Percentage of participants with anti-CNCT19 antibodies in serum
To characterize prevalence and incidence of humoral immunogenicity to CNCT19
Time frame: 2 years