Acute Lymphoblastic Leukemia, in Relapse, Acute Lymphocytic Leukaemia Refractory, Multiple Myeloma in Relapse, Multiple Myeloma, Refractory, Non-Hodgkin's Lymphoma Refractory, Non-Hodgkin's Lymphoma, Relapsed
Conditions
Keywords
Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma, Multiple Myeloma, CAR T-cell therapy, Dasatinib
Brief summary
A Study of CD19/BCMA-targeted CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia, B-cell Non-Hodgkin's Lymphoma and Multiple Myeloma.
Detailed description
This is a double-arm, single-center study. This study is indicated for relapsed and/or refractory B-cell acute lymphoblastic leukemia, B-cell non-Hodgkin's lymphoma and multiple myeloma, the selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 120 patients will be enrolled for this trial. Primary objective is to explore the safety.
Interventions
DRUGCD19/BCMA Targeted CAR T-cells and dasatinib
Each subject receive CS1 Targeted CAR T-cells by intravenous infusion, and the dasatinib was combined according to the presumed regimens.
DRUGCD19/BCMA Targeted CAR T-cells
Each subject receive CS1 Targeted CAR T-cells by intravenous infusion.
Sponsors
Yake Biotechnology Ltd.
Zhejiang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed diagnosis of CD19+ ALL, CD19+ NHL, or BCMA+ MM per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines (2020.v2); 2. Relapsed or refractory B cell hematological malignancies (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; 5. Relapse after hematopoietic stem cell transplantation; 6. Extramedullary leisions which were ineffective to radiotherapy or chemotherapy; 3. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L; 4. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%; 5. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%; 6. Estimated survival time ≥ 12 weeks; 7. ECOG performance status 0 to 2; 8. Women of childbearing age had negative pregnancy test during screening period and before administration, and agreed to take effective contraceptive measures at least one year after infusion. 9. Patients 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 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 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 CAR-T cells infusion | From the first infusion of CAR-T cells to the occurrence of any event, including death, relapse orgene 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 |
| Multiple myeloma (MM), Overall response rate (ORR) | At Day 28 | Assessment of ORR at Day 28 |
| 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 |
| Quality of life | At Baseline, Month 1, 3, 6, 9 and 12 | Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale \[For item1-28: max score: 112, min score: 28, higher scores mean a better outcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome\] to measure Quality of life at Baseline, Month 1, 3, 6, 9 and 12 |
| Activities of Daily Living (ADL) score | At Baseline, Month 1, 3, 6, 9 and 12 | Assessment using Activities of Daily Living (ADL) scale (Barthel Index) \[max score: 100, min score: 0, higher scores mean a better outcome\] at Baseline, Month 1, 3, 6, 9 and 12 |
| Instrumental Activities of Daily Living (IADL) score | At Baseline, Month 1, 3, 6, 9 and 12 | Assessment of Instrumental Activities of Daily Living (IADL) scale \[max score: 56, min score: 14, higher scores mean a worse outcome\] at Baseline, Month 1, 3, 6, 9 and 12 |
| Hospital Anxiety and Depression Scale (HADS) score | At Baseline, Month 1, 3, 6, 9 and 12 | Assessment using Hospital Anxiety and Depression Scale (HADS) \[max score: 42, min score: 0, higher scores mean a worse outcome\] at Baseline, Month 1, 3, 6, 9 and 12 |
| MM, Overall survival (OS) | At Month 6, 12, 24 | Assessment of OS at Month 6, 12, 24 |
| B-ALL, Overall survival (OS) | Up to 2 years after CAR-T cells infusion | From the first infusion of CAR-T cells to death or the last visit |
Countries
China
Contacts
Primary ContactHe Huang, PhD
Backup ContactYongxian Hu, PhD
Outcome results
None listed