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

B-cell Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05667506
• Other study ID #: HY001103
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 7, 2023
• Est. completion date: December 30, 2025

Study information

• Verified date: September 2023
• Source: Juventas Cell Therapy Ltd.
• Contact: Hui Ding
• Phone: +86-010-65960098
• Email: dinghui[@]juventas.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 47
• Est. completion date: December 30, 2025
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• B-cell Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• single dose of CNCT19
Autologous 2nd generation CD19-directed CAR-T cells, single infusion intravenously. Lymphodepletion treatment: Drugs:Fludarabine Drugs: Cyclophosphamide

Locations

Country	Name	City	State
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	The Second Hospital of Anhui Medical University	Hefei	Anhui
China	The First Affilicated Hospital of Nanchang University	Nanchang	Jiangxi
China	Children's Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	Institute of Hematology & Blood Diseases Hospital	Tianjin	Tianjin
China	Union Hospital Tongji Medical College Huazhong University of Science of Technology	Wuhan	Hubei
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Juventas Cell Therapy Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Best overall response (BOR)	The proportion of patients who have achieved the best response (CR or CRi) after CNCT19 treatment	up to 2 years
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	Treatment-Emergent Adverse Events	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE) and Severity of TEAE	up to 2 years
Secondary	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)
Secondary	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)
Secondary	Pharmacokinetic (PK)- Cmax of CNCT19	Maximum detected concentration of CNCT19 in peripheral blood	Up to 2 years
Secondary	Pharmacokinetic (PK)- Tmax of CNCT19.	Time to maximum concentration of CNCT19 in peripheral blood	Up to 2 years
Secondary	Pharmacokinetic (PK)- AUC of CNCT19.	Area under the concentration (AUC) vs time curve of CNCT19 in peripheral blood	Up to 2 years
Secondary	Concentration of Cytokines in Serum	Collected as pharmacodynamic data, including IL-6 at least	28 days
Secondary	Percentage of participants with anti-CNCT19 antibodies in serum	To characterize prevalence and incidence of humoral immunogenicity to CNCT19	2 years