A Study of CNCT19 Treatment in Children and Adolescent r/r ALL Patients(Pediatric)
- Conditions
- B-cell Acute Lymphoblastic Leukemia
- Interventions
- Registration Number
- NCT05667506
- Lead Sponsor
- Juventas Cell Therapy Ltd.
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 47
- Signed written informed consent prior to any study procedures (patient and/or parent or legal guardian)
- Age 3 to 18. Weight ≥10kg
- Relapsed or refractory acute lymphoblastic leukemia (ALL).
- Documentation of CD19 tumor expression demonstrated in bone marrow or peripheral blood within 3 months before screening.
- Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
- Karnofsky (age ≥ 16 years) performance status ≥ 70 or Lansky (age < 16 years) performance status ≥ 50 at screening
- Organ function requirements: All patients must have adequate renal and liver functions
Key
-
Active Central Nervous System (CNS) involvement by malignancy.
-
Isolated extra-medullary disease relapse.
-
Patients with Burkitt's lymphoma/leukemia, mixed phenotypic acute leukemia and Chronic Myelogenous Leukemia in Blast Crisis
-
History of concomitant genetic syndrome
-
Patients with acute graft-versus-host disease (GVHD) or moderate-to-severe chronic GVHD within 4 weeks before screening.
-
Active systemic autoimmune disease
-
Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti-HCV positive).
-
Patients with active infections at screening.
-
Patients who received specified chemotherapy before CNCT19 infusion
-
Radiotherapy before CNCT19 infusion:
Non-CNS site of radiation completed < 4 weeks prior to CNCT19 Infusion; CNS directed radiation completed < 8 weeks prior to CNCT19 infusion.
-
Donor lymphocyte infusion (DLI) must be stopped > 6 week prior to CNCT19 infusion.
-
Has had treatment with any prior CAR-T therapy.
-
Life expectancy < 3 months.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Single dose of CNCT19 single dose of CNCT19 A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CNCT19.
- Primary Outcome Measures
Name Time Method Overall Remission Rate (ORR) within 3 months 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)
- Secondary Outcome Measures
Name Time Method Duration of remission (DOR) to data cutoff date 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
Allogeneic Stem Cell Transplant (Allo-SCT) rate First infusion date of CNCT19 to data cutoff date(up to 2 years) The proportion of patients who have received Allo-SCT after CNCT19 treatment
Relapse Free Survival (RFS) 2 years RFS is defined as the time from the CNCT19 infusion date to the date of disease relapse or death from any cause.
Overall complete Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators within 3 months MRD negativity status as determined using flow cytometry
In vivo cellular Pharmacokinetic (PK) profile of CNCT19 Up to 3 months(BM sample); Up to 2 years(Blood sample) 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).
Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators at the end of Month 3 MRD negativity as determined using flow cytometry
Best overall response (BOR) up to 2 years The proportion of patients who have achieved the best response (CR or CRi) after CNCT19 treatment
Pharmacokinetic (PK)- Cmax of CNCT19 Up to 2 years Maximum detected concentration of CNCT19 in peripheral blood
Percentage of participants with anti-CNCT19 antibodies in serum 2 years To characterize prevalence and incidence of humoral immunogenicity to CNCT19
Overall survival (OS) 2 years OS is defined as the time from the CNCT19 Cell Injection infusion to the date of death from any cause
Treatment-Emergent Adverse Events up to 2 years Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE) and Severity of TEAE
Concentration of Cytokines in Serum 28 days Collected as pharmacodynamic data, including IL-6 at least
Overall Remission Rate (ORR) as determined by IRC and Investigators at the end of month 3 The Investigators' evaluation results of ORR will be utilized in the sensitivity analysis
Pharmacokinetic (PK)- Tmax of CNCT19. Up to 2 years Time to maximum concentration of CNCT19 in peripheral blood
Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities From CNCT19 infusion to date of data cutoff (maximum: 2 years) Clinically significant laboratory abnormalities were defined as per investigator's discretion
Pharmacokinetic (PK)- AUC of CNCT19. Up to 2 years Area under the concentration (AUC) vs time curve of CNCT19 in peripheral blood
Trial Locations
- Locations (9)
The Second Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Children's Hospital of Chongqing Medical University
🇨🇳Chongqing, Chongqing, China
Guangzhou Women and Children's Medical Center
🇨🇳Guangzhou, Guangdong, China
Nanfang Hospital
🇨🇳Guangzhou, Guangdong, China
Union Hospital Tongji Medical College Huazhong University of Science of Technology
🇨🇳Wuhan, Hubei, China
Children's Hospital of Nanjing Medical University
🇨🇳Nanjing, Jiangsu, China
The Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, Jiangsu, China
The First Affilicated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Institute of Hematology & Blood Diseases Hospital
🇨🇳Tianjin, Tianjin, China