A Study of CNCT19 Treatment in Children and Adolescent r/r ALL Patients(Pediatric)

A Phase Ib/II, Single Arm, Multi-center Study Evaluating the Safety and Efficacy of CNCT19 in Children and Adolescent(Pediatric) Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r B-ALL)

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).

Study Overview

• Status: Recruiting
• Conditions: B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Biological: single dose of CNCT19

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.

• Study Type: Interventional
• Enrollment (Estimated): 47
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Hui Ding; Phone Number: +86-010-65960098; Email: dinghui@juventas.cn

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Not yet recruiting
      • The Second Hospital of Anhui Medical University
      • Contact: Ningling Wang, Dr.
  • Chongqing
    • Chongqing, Chongqing, China
      • Recruiting
      • Children's Hospital of Chongqing Medical University
      • Contact: Xianmin Guan, Dr.
  • Guangdong
    • Guangzhou, Guangdong, China
      • Not yet recruiting
      • Nanfang Hospital
      • Contact: Hongsheng Zhou, Dr.
    • Guangzhou, Guangdong, China
      • Recruiting
      • Guangzhou Women And Children's Medical Center
      • Contact: Yingyi He, Dr.
  • Hubei
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Union Hospital Tongji Medical College Huazhong University of Science of Technology
      • Contact: Heng Mei, Dr.
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Children's Hospital of Nanjing Medical University
      • Contact: Yongjun Fang, Dr.
    • Xuzhou, Jiangsu, China
      • Recruiting
      • The Affiliated Hospital of Xuzhou Medical University
      • Contact: Kailin Xu, Dr.
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Recruiting
      • The First Affilicated Hospital of Nanchang University
      • Contact: Fei Li, Dr.
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital
      • Contact: Xiaofan Zhu, MD; Phone Number: +86-010-65960098; Email: xfzhu@ihcams.ac.cn
      • Contact: Xiaoming Liu, MD; Phone Number: +86-010-65960098; Email: liuxiaoming@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Signed written informed consent prior to any study procedures (patient and/or parent or legal guardian)
2. Age 3 to 18. Weight ≥10kg
3. Relapsed or refractory acute lymphoblastic leukemia (ALL).
4. Documentation of CD19 tumor expression demonstrated in bone marrow or peripheral blood within 3 months before screening.
5. Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
6. Karnofsky (age ≥ 16 years) performance status ≥ 70 or Lansky (age < 16 years) performance status ≥ 50 at screening
7. Organ function requirements: All patients must have adequate renal and liver functions

Key Exclusion Criteria:

1. Active Central Nervous System (CNS) involvement by malignancy.
2. Isolated extra-medullary disease relapse.
3. Patients with Burkitt's lymphoma/leukemia, mixed phenotypic acute leukemia and Chronic Myelogenous Leukemia in Blast Crisis
4. History of concomitant genetic syndrome
5. Patients with acute graft-versus-host disease (GVHD) or moderate-to-severe chronic GVHD within 4 weeks before screening.
6. Active systemic autoimmune disease
7. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti-HCV positive).
8. Patients with active infections at screening.
9. Patients who received specified chemotherapy before CNCT19 infusion

10. 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.

11. Donor lymphocyte infusion (DLI) must be stopped > 6 week prior to CNCT19 infusion.
12. Has had treatment with any prior CAR-T therapy.
13. Life expectancy < 3 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose of CNCT19; A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CNCT19.	Biological: single dose of CNCT19; Autologous 2nd generation CD19-directed CAR-T cells, single infusion intravenously. Lymphodepletion treatment: Drugs:Fludarabine Drugs: Cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall 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)	within 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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	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	to data cutoff date
Allogeneic Stem Cell Transplant (Allo-SCT) rate	The proportion of patients who have received Allo-SCT after CNCT19 treatment	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.	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	2 years
Treatment-Emergent Adverse Events	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE) and Severity of TEAE	up to 2 years
Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities	Clinically significant laboratory abnormalities were defined as per investigator's discretion	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).	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	Up to 2 years
Pharmacokinetic (PK)- Tmax of CNCT19.	Time to maximum concentration of CNCT19 in peripheral blood	Up to 2 years
Pharmacokinetic (PK)- AUC of CNCT19.	Area under the concentration (AUC) vs time curve of CNCT19 in peripheral blood	Up to 2 years
Concentration of Cytokines in Serum	Collected as pharmacodynamic data, including IL-6 at least	28 days
Percentage of participants with anti-CNCT19 antibodies in serum	To characterize prevalence and incidence of humoral immunogenicity to CNCT19	2 years

Collaborators and Investigators

• Sponsor: Juventas Cell Therapy Ltd.
• Investigators: Principal Investigator: Xiaofan Zhu, M.D, Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2023
• Primary Completion (Actual): May 30, 2025
• Study Completion (Estimated): May 30, 2027

Study Registration Dates

• First Submitted: December 5, 2022
• First Submitted That Met QC Criteria: December 19, 2022
• First Posted (Actual): December 28, 2022

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: CNCT19; Cluster of differentiation antigen 19(CD19); CD19-directed CAR-T cells
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: HY001103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Currently the investigators have no plan of interim anaylsis, the investigators don't plan to share individual participant data(IPD) during the trial on-going.

Drug and device information, study documents

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