B-cell Acute Lymphoblastic Leukemia
Conditions
Keywords
CNCT19, Cluster of differentiation antigen 19(CD19), CD19-directed CAR-T cells
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.
Interventions
BIOLOGICALsingle dose of CNCT19
Autologous 2nd generation CD19-directed CAR-T cells, single infusion intravenously. Lymphodepletion treatment: Drugs:Fludarabine Drugs: Cyclophosphamide
Sponsors
Juventas Cell Therapy Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 18 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| Treatment-Emergent Adverse Events | up to 2 years | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE) and Severity of TEAE |
Countries
China
Contacts
Primary ContactHui Ding
Outcome results
None listed