Relapsed and/or Refractory Acute Lymphoblastic Leukemia, Relapsed and/or Refractory B-cell Non-Hodgkin's Lymphoma
Conditions
Brief summary
A study of CD79b CAR-T Cell Therapy for Patients With Relapsed and/or Refractory 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 Relapsed and/or Refractory Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 72 patients will be enrolled. Primary objective is to explore the safety, main consideration is dose-related safety.
Interventions
DRUGCD79b CAR-T Cells
Each subject receive CD79b CAR-Tcells 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
Healthy volunteers
No
Inclusion criteria
* Only For B-ALL 1. No gender or age limit 2. Histologically confirmed diagnosis of CD69b+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Myeloid Leukemia (2016.v1); 3. Relapsed or refractory CD123+ AML (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 in bone marrow is \> 5% (by morphology), and/or \> 0.01% (by flowcytometry); 5. Philadelphia chromosome negative(Ph-) subjects; Ph+ subjects who cannot tolerate tyrosine kinase inhibitor (TKI) treatment or who do not respond to two kinds of TKI treatment; * Only For B-NHL 1. No gender or age limit; 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 * For both B-ALL and B-NHL 1. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, 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 indoorair 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 studyand sign the informed consent.
Exclusion criteria
* 1\. History of craniocerebral trauma, conscious disturbance,epilepsy,cerebrovascular ischemia, and cerebrovascular, hemorrhagicdiseases; 2. Electrocardiogram shows prolonged QT interval, severe heart diseasessuch as severe arrhythmia in the past; 3. Pregnant (or lactating) women; 4. Patients with severe active infections (excluding simple urinarytractinfectionand bacterial pharyngitis); 5. Active infection of hepatitis B virus or hepatitis C virus; 6. Previously treated with any CAR-T cell product or other genetically modified T cell therapies; 7. Insufficient amplification capacity in response to CD3 / CD28 co-stimulus signal (\<5 times) 8. Creatinine\>2.5mg/dl, or ALT / AST \> 3 times of normal amounts, or bilirubin\>2.0 mg/dl; 9. Other uncontrolled diseases that were not suitable for this trial; 10. Patients with HIV infection; 11. Any situations that the investigator believes may increase the risk ofpatients or interfere with the results of study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) | Baseline up to 28 days after CD79b 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 CD79b targeted CAR T-cells infusion | Incidence of treatment-emergent adverse events \[Safety and Tolerability\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Lymphoblastic Leukemia (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 |
| ALL, Overall survival（OS） | Up to 2 years after CD79b CAR-T cells infusion | From the first infusion of CD79b CAR-T cells to death or the last visit |
| ALL, Event-free survival (EFS) | Up to 2 years after CD79b CAR-T cells infusion | From the first infusion of CD79b CAR-T cells to the occurrence of any event, including death, relapse or generelapse, disease progression (any one occurs first), and the last visit |
| B-cell Non-Hodgkin's Lymphoma（B-NHL）, 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 |
| B-NHL, Overall survival（OS） | Up to 2 years after CD79b CAR-T cells infusion | From the first infusion of CD79b CAR-T cells to death or the last visit |
| B-NHL, Event-free survival (EFS) | Up to 2 years after CD79b CAR-T cells infusion | From the first infusion of CD79b CAR-T cells to the occurrence of any event, including death, relapse or generelapse, disease progression (any one occurs first), and the last visit |
| Quality of life(EORTC QLQ-C30) Core 30 (EORTC QLQ-C30) | 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 |
Countries
China
Contacts
Primary ContactHe Huang, PhD
Backup ContactYongxian Hu, PhD
Outcome results
None listed