Acute Lymphoblastic Leukemia, Non-hodgkin Lymphoma,B Cell
Conditions
Keywords
Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma, CAR T-cell therapy
Brief summary
A Study of Humanized CD19 CAR-T Cells Therapy for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma.
Detailed description
This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory CD19+ B-cell hematological malignancies, including acute lymphoblastic leukemia and B-cell non-Hodgkin's lymphoma. The selections of dose levels and the numberof subjects are based on clinical trials of similar foreign products. Two groups of patients will be enrolled, 36 in each group. Primary objective is to explore the safety, main consideration is dose-related safety.
Interventions
DRUGHumanized CD19 CAR-T cells
Each subject receive humanized CD19 CAR T-cells by intravenous infusion
Sponsors
Yake Biotechnology Ltd.
Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Inclusion criteria only for B-ALL: 1. Male or female aged 3-70 years; 2. Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1); 3. Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions): 1. CR not achieved after standardized chemotherapy; 2. CR achieved following the first induction, but CR duration is less than 12 months; 3. Ineffectively after first or multiple remedial treatments; 4. 2 or more relapses; 4. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is \>5% (by morphology), and/or \>1% (by flow cytometry); 5. Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments; * Inclusion criteria only for B-NHL: 1. Male or female aged 18-75 years; 2. Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma (2016); 3. Relapsed or refractory B-NHL (meeting one of the following conditions): 1. No response or relapse after second-line or above chemotherapy regimens; 2. Primary drug resistance; 3. Relapse after auto-HSCT; 4. At least one assessable tumor lesion per Lugano 2014 criteria; * Common inclusion criteria for B-ALL and B-NHL: 1. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L; 2. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%; 3. No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%; 4. Estimated survival time ≥ 3 months; 5. ECOG performance status 0 to 2; 6. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.
Exclusion criteria
Subjects with any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) | Baseline up to 28 days after humanized CD19 targeted CAR T-cells infusion | Adverse events assessed according to NCI-CTCAE v5.0 criteria |
| Incidence of treatment-emergent adverse events (TEAEs) | Up to 2 years after humanized CD19 targeted CAR T-cells infusion | Incidence of treatment-emergent adverse events \[Safety and Tolerability\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| B-ALL, Event-free survival (EFS) | Up to 2 years after humanized CD19 CAR-T cells infusion | From the first infusion of humanized CD19 CAR-T cells to the occurrence of any event, including death, relapse or gene relapse, disease progression (any one occurs first), and the last visit |
| B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR) | At Week 4, 12, and Month 6, 12, 18, 24 | Assessment of ORR (ORR = CR + PR) per Lugano 2014 criteria |
| B-NHL, disease control rate (DCR) | At Week 12 and Month 6, 12, 18, 24 | Assessment of DCR (DCR=CR+PR+SD) per Lugano 2014 criteria |
| B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR) | At Month 1, 3, 6, 12, 18 and 24 | Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24 |
| IADL score | At Baseline, Month 1, 3, 6, 9 and 12 | Assessment of IADL score at Baseline, Month 1, 3, 6, 9 and 12 |
| ADL score | At Baseline, Month 1, 3, 6, 9 and 12 | Assessment of ADL score at Baseline, Month 1, 3, 6, 9 and 12 |
| HADS score | At Baseline, Month 1, 3, 6, 9 and 12 | Assessment of Hospital Anxiety and Depression Scale (HADS) score at Baseline, Month 1, 3, 6, 9 and 12 |
| Quality of life | At Baseline, Month 1, 3, 6, 9 and 12 | Assessment of Quality of life using Research and Treatment of Cancer QOL Core Questionnaire 30 (EORTC QLQ-30) at Baseline, Month 1, 3, 6, 9 and 12 |
| B-ALL, Overall survival (OS) | Up to 2 years after humanized CD19 CAR-T cells infusion | From the first infusion of humanized CD19 CAR-T cells to death or the last visit |
Countries
China
Contacts
Primary ContactHe Huang, PhD
Backup ContactYongxian Hu, PhD
Outcome results
None listed