Acute Myeloid Leukemia, Multiple Myeloma, Non-hodgkin's Lymphoma
Conditions
Keywords
CAR T-cell therapy, CD70, Acute Myeloid Leukemia, Non-Hodgkin's lymphoma, Multiple Myeloma
Brief summary
A Study of CD 70 CAR T for patients with CD70 positive malignant hematologic diseases
Detailed description
This is a single arm, open-label, single-center study. This study is indicated for CD 70 CAR T for patients with CD70 positive malignant hematologic diseases. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 108 patients will be enrolled. Primary objective is to explore the safety,main consideration is dose-related safety.
Interventions
BIOLOGICALCD70 CAR T-cells
Each subject receive CD70 CAR T-cells by intravenous infusion
Sponsors
Yake Biotechnology Ltd.
Zhejiang University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Inclusion criteria only for AML: 1. Histologically confirmed diagnosis of CD70 AML per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Myeloid Leukemia (2016.v1); 2. Relapsed or refractory CD70+ 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; 3. The number of primordial cells in bone marrow is \> 5% (by morphology), and/or \> 0.01% (by flowcytometry); 4. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L; 5. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%; 6. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%; 7. Estimated survival time ≥ 3 months; 8. ECOG performance status 0 to 2; 9. Patients or their legal guardians volunteer to participate in the studyand sign the informed consent. Inclusion criteria only for NHL: 1. No gender and 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 CD70+ 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 Inclusion criteria only for MM: 1. Histologically confirmed diagnosis of CD70 multiple myeloma (MM)： 1. According to the diagnostic criteria of IMWG multiple myeloma, the diagnosis was recurrent / refractory multiple myeloma 2. Cases with recurrent positive minimal residual disease; 3. Extramedullary leision which is hard to be eradicated by chemotherapy or radiotherapy. 2. No gender and age limit; 3. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, 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 ≥ 3 months; 7. ECOG performance status 0 to 2; 8. Patients or their legal guardians volunteer to participate in the studyand sign the informed consent. Common inclusion criteria : 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
1. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases; 2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past; 3. Pregnant (or lactating) women; 4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis); 5. Active infection of hepatitis B virus or hepatitis C virus; 6. Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving inhaled steroids; 7. Previously treated with any CAR-T cell product or other geneticallymodified T cell therapies; 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 of patients or interfere with the results of study. -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) | Baseline up to 28 days after CD70 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 CD70 targeted CAR T-cells infusion | Incidence of treatment-emergent adverse events \[Safety and Tolerability\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AML, Event-free survival (EFS) | Up to 2 years after CD70 CAR-T cells infusion | From the first infusion of CD70 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 |
| Non-Hodgkin's lymphoma (NHL), Overall response rate (ORR) | At Month 1, 3, 6, 12, 18 and 24 | Assessment of ORR (ORR = CR + CRi) at Month 1, 3, 6, 12, 18 and 24 |
| NHL, Overall survival (OS) | Up to 2 years after CD70 CAR-T cells infusion | From the first infusion of CD70 CAR-T cells to death or the last visit |
| NHL, Event-free survival (EFS) | Up to 2 years after CD70 CAR-T cells infusion | From the first infusion of CD70 CAR-T cells to the occurrence of any event, including death, relapse or gene relapse, |
| Multiple myeloma (MM), Overall response rate (ORR) | At Month 1, 3, 6, 12, 18 and 24 | Assessment of ORR (ORR = CR + CRi) at Month 1, 3, 6, 12, 18 and 24 |
| Acute Myeloid Leukemia (AML), Overall response rate (ORR) | At Month 1, 3, 6, 12, 18 and 24 | Assessment of ORR (ORR = CR + CRi) at Month 1, 3, 6, 12, 18 and 24 |
| MM, Event-free survival (EFS) | Up to 2 years after CD70 CAR-T cells infusion | From the first infusion of CD70 CAR-T cells to the occurrence of any event, including death, relapse or gene relapse |
| 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) | Up to 2 years after CD70 CAR-T cells infusion | From the first infusion of CD70 CAR-T cells to death or the last visit |
| AML, Overall survival (OS) | Up to 2 years after CD70 CAR-T cells infusion | From the first infusion of CD70 CAR-T cells to death or the last visit |
Countries
China
Contacts
Primary ContactHe Huang, PhD
Backup ContactYongxian Hu, PhD
Outcome results
None listed