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

Sponsor

Juventas Cell Therapy Ltd. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05667506

Collaborator

(none)

Enrollment

Arm

35.8

Anticipated Duration (Months)

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
B-cell Acute Lymphoblastic Leukemia	Biological: single dose of CNCT19	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

47 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Jan 6, 2023

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Dec 30, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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
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
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
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 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
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
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).
Pharmacokinetic (PK)- Cmax of CNCT19 [Up to 2 years]
Maximum detected concentration of CNCT19 in peripheral blood
Pharmacokinetic (PK)- Tmax of CNCT19. [Up to 2 years]
Time to maximum concentration of CNCT19 in peripheral blood
Pharmacokinetic (PK)- AUC of CNCT19. [Up to 2 years]
Area under the concentration (AUC) vs time curve of CNCT19 in peripheral blood
Concentration of Cytokines in Serum [28 days]
Collected as pharmacodynamic data, including IL-6 at least
Percentage of participants with anti-CNCT19 antibodies in serum [2 years]
To characterize prevalence and incidence of humoral immunogenicity to CNCT19

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

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 Exclusion Criteria:

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.