Back to resultsA Study of CNCT19 Treatment in Children and Adolescent r/r ALL Patients(Pediatric)
Primary Purpose
B-cell Acute Lymphoblastic Leukemia
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
single dose of CNCT19
Sponsored by
About this trial
This is an interventional treatment trial for B-cell Acute Lymphoblastic Leukemia focused on measuring CNCT19, Cluster of differentiation antigen 19(CD19), CD19-directed CAR-T cells
Eligibility Criteria
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.
Sites / Locations
- The Second Hospital of Anhui Medical University
- Children's Hospital of Chongqing Medical UniversityRecruiting
- Guangzhou Women and Children's Medical CenterRecruiting
- Nanfang Hospital
- Union Hospital Tongji Medical College Huazhong University of Science of Technology
- Children's Hospital of Nanjing Medical UniversityRecruiting
- The Affiliated Hospital of Xuzhou Medical UniversityRecruiting
- The First Affilicated Hospital of Nanchang UniversityRecruiting
- Institute of Hematology & Blood Diseases HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single dose of CNCT19
Arm Description
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CNCT19.
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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
Overall Remission Rate (ORR) as determined by IRC and Investigators
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
MRD negativity as determined using flow cytometry
Best overall response (BOR)
The proportion of patients who have achieved the best response (CR or CRi) after CNCT19 treatment
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
Allogeneic Stem Cell Transplant (Allo-SCT) rate
The proportion of patients who have received Allo-SCT after CNCT19 treatment
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.
Overall survival (OS)
OS is defined as the time from the CNCT19 Cell Injection infusion to the date of death from any cause
Treatment-Emergent Adverse Events
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE) and Severity of TEAE
Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities
Clinically significant laboratory abnormalities were defined as per investigator's discretion
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).
Pharmacokinetic (PK)- Cmax of CNCT19
Maximum detected concentration of CNCT19 in peripheral blood
Pharmacokinetic (PK)- Tmax of CNCT19.
Time to maximum concentration of CNCT19 in peripheral blood
Pharmacokinetic (PK)- AUC of CNCT19.
Area under the concentration (AUC) vs time curve of CNCT19 in peripheral blood
Concentration of Cytokines in Serum
Collected as pharmacodynamic data, including IL-6 at least
Percentage of participants with anti-CNCT19 antibodies in serum
To characterize prevalence and incidence of humoral immunogenicity to CNCT19
Full Information
NCT ID
NCT05667506
First Posted
December 5, 2022
Last Updated
September 19, 2023
Sponsor
Juventas Cell Therapy Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05667506
Brief Title
A Study of CNCT19 Treatment in Children and Adolescent r/r ALL Patients(Pediatric)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 7, 2023 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Juventas Cell Therapy Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Acute Lymphoblastic Leukemia
Keywords
CNCT19, Cluster of differentiation antigen 19(CD19), CD19-directed CAR-T cells
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
47 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Single dose of CNCT19
Arm Type
Experimental
Arm Description
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CNCT19.
Intervention Type
Biological
Intervention Name(s)
single dose of CNCT19
Intervention Description
Autologous 2nd generation CD19-directed CAR-T cells, single infusion intravenously.
Lymphodepletion treatment:
Drugs:Fludarabine Drugs: Cyclophosphamide
Primary Outcome Measure Information:
Title
Overall Remission Rate (ORR)
Description
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
Secondary Outcome Measure Information:
Title
Overall complete Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators
Description
MRD negativity status as determined using flow cytometry
Time Frame
within 3 months
Title
Overall Remission Rate (ORR) as determined by IRC and Investigators
Description
The Investigators' evaluation results of ORR will be utilized in the sensitivity analysis
Time Frame
at the end of month 3
Title
Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators
Description
MRD negativity as determined using flow cytometry
Time Frame
at the end of Month 3
Title
Best overall response (BOR)
Description
The proportion of patients who have achieved the best response (CR or CRi) after CNCT19 treatment
Time Frame
up to 2 years
Title
Duration of remission (DOR)
Description
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
Title
Allogeneic Stem Cell Transplant (Allo-SCT) rate
Description
The proportion of patients who have received Allo-SCT after CNCT19 treatment
Time Frame
First infusion date of CNCT19 to data cutoff date(up to 2 years)
Title
Relapse Free Survival (RFS)
Description
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
Title
Overall survival (OS)
Description
OS is defined as the time from the CNCT19 Cell Injection infusion to the date of death from any cause
Time Frame
2 years
Title
Treatment-Emergent Adverse Events
Description
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE) and Severity of TEAE
Time Frame
up to 2 years
Title
Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities
Description
Clinically significant laboratory abnormalities were defined as per investigator's discretion
Time Frame
From CNCT19 infusion to date of data cutoff (maximum: 2 years)
Title
In vivo cellular Pharmacokinetic (PK) profile of CNCT19
Description
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)
Title
Pharmacokinetic (PK)- Cmax of CNCT19
Description
Maximum detected concentration of CNCT19 in peripheral blood
Time Frame
Up to 2 years
Title
Pharmacokinetic (PK)- Tmax of CNCT19.
Description
Time to maximum concentration of CNCT19 in peripheral blood
Time Frame
Up to 2 years
Title
Pharmacokinetic (PK)- AUC of CNCT19.
Description
Area under the concentration (AUC) vs time curve of CNCT19 in peripheral blood
Time Frame
Up to 2 years
Title
Concentration of Cytokines in Serum
Description
Collected as pharmacodynamic data, including IL-6 at least
Time Frame
28 days
Title
Percentage of participants with anti-CNCT19 antibodies in serum
Description
To characterize prevalence and incidence of humoral immunogenicity to CNCT19
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hui Ding
Phone
+86-010-65960098
Email
dinghui@juventas.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaofan Zhu, M.D
Organizational Affiliation
Institute of Hematology & Blood Diseases Hospital, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Second Hospital of Anhui Medical University
City
Hefei
State/Province
Anhui
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ningling Wang, Dr.
Facility Name
Children's Hospital of Chongqing Medical University
City
Chongqing
State/Province
Chongqing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xianmin Guan, Dr.
Facility Name
Guangzhou Women and Children's Medical Center
City
Guangzhou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yingyi He, Dr.
Facility Name
Nanfang Hospital
City
Guangzhou
State/Province
Guangdong
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hongsheng Zhou, Dr.
Facility Name
Union Hospital Tongji Medical College Huazhong University of Science of Technology
City
Wuhan
State/Province
Hubei
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heng Mei, Dr.
Facility Name
Children's Hospital of Nanjing Medical University
City
Nanjing
State/Province
Jiangsu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yongjun Fang, Dr.
Facility Name
The Affiliated Hospital of Xuzhou Medical University
City
Xuzhou
State/Province
Jiangsu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kailin Xu, Dr.
Facility Name
The First Affilicated Hospital of Nanchang University
City
Nanchang
State/Province
Jiangxi
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fei Li, Dr.
Facility Name
Institute of Hematology & Blood Diseases Hospital
City
Tianjin
State/Province
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaofan Zhu, MD
Phone
+86-010-65960098
Email
xfzhu@ihcams.ac.cn
First Name & Middle Initial & Last Name & Degree
Xiaoming Liu, MD
Phone
+86-010-65960098
Email
liuxiaoming@ihcams.ac.cn
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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.
Learn more about this trial
A Study of CNCT19 Treatment in Children and Adolescent r/r ALL Patients(Pediatric)
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