Clinical trial NCT05667506: 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
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-cell Acute Lymphoblastic Leukemia
Keywords: CNCT19
Cluster of differentiation antigen 19(CD19)
CD19-directed CAR-T cells
Lead sponsor: Juventas Cell Therapy Ltd.
Sponsor class: INDUSTRY
First posted: 2022-12-28
Enrollment: 47
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Remission Rate (ORR)
timeFrame: within 3 months
Secondary outcomes:
measure: Overall complete Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators
timeFrame: within 3 months
measure: Overall Remission Rate (ORR) as determined by IRC and Investigators
timeFrame: at the end of month 3
measure: Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators
timeFrame: at the end of Month 3
measure: Best overall response (BOR)
timeFrame: up to 2 years
measure: Duration of remission (DOR)
timeFrame: to data cutoff date
measure: Allogeneic Stem Cell Transplant (Allo-SCT) rate
timeFrame: First infusion date of CNCT19 to data cutoff date(up to 2 years)
measure: Relapse Free Survival (RFS)
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 2 years
measure: Treatment-Emergent Adverse Events
timeFrame: up to 2 years
measure: Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities
timeFrame: From CNCT19 infusion to date of data cutoff (maximum: 2 years)
measure: In vivo cellular Pharmacokinetic (PK) profile of CNCT19
timeFrame: Up to 3 months(BM sample); Up to 2 years(Blood sample)
measure: Pharmacokinetic (PK)- Cmax of CNCT19
timeFrame: Up to 2 years
measure: Pharmacokinetic (PK)- Tmax of CNCT19.
timeFrame: Up to 2 years
measure: Pharmacokinetic (PK)- AUC of CNCT19.
timeFrame: Up to 2 years
measure: Concentration of Cytokines in Serum
timeFrame: 28 days
measure: Percentage of participants with anti-CNCT19 antibodies in serum
timeFrame: 2 years
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Chongqing
country: China
facility: Children's Hospital of Chongqing Medical University
state: Chongqing
city: Guangzhou
country: China
facility: Guangzhou Women and Children's Medical Center
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science of Technology
state: Hubei
city: Nanjing
country: China
facility: Children's Hospital of Nanjing Medical University
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affilicated Hospital of Nanchang University
state: Jiangxi
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Xiaofan Zhu, M.D
role: PRINCIPAL_INVESTIGATOR
References: