Hematological Malignancies, Infectious Diseases
Conditions
Keywords
Infectious diseases, Hematological Malignancies, CAR T-cell therapy, LMP1
Brief summary
A study of LMP1 CAR-T for patients with LMP1 positive infectious diseases and hematological malignancies
Detailed description
This is a single arm, open-label, single-center study. This study is indicated for LMP1 positive infectious diseases and hematological malignancies. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 144 patients will be enrolled. Primary objective is to explore the safety, main consideration is dose-related safety.
Interventions
DRUGLMP1 CAR T-cells
Each subject receive LMP1 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
Healthy volunteers
No
Inclusion criteria
Only applicable to the inclusion criteria of CAEBV 1. Subjects who are diagnosed with CAEBV according to the Okano revised standard proposed by the Japanese Ministry of Health, Labour and Welfare Research Group for the Prevention of Refractory Diseases; 2. All CAEBV patients who have not achieved complete remission, including: 1. Active phase: EBV-DNA level in PBMC is higher than 1×10\^2.5 copies/μg DNA, with symptoms and signs of active diseases such as fever, hepatomegaly, splenomegaly, abnormal liver function, decrease of blood three lines, lymphadenopathy, and progressive skin lesions with increased EBV titer in peripheral blood; 2. inactive phase: EBV-DNA level in PBMC is higher than 1×10\^2.5 copies/μg DNA, without symptoms and signs of active diseases; 3. The disease has not yet progressed to hematopoietic lymphohistiocytosis (HLH); Only applicable to the inclusion criteria of LMP1-positive ENKTL: 1. According to the 2016 WHO classification criteria for lymphocytic tumors: Subjects diagnosed by histopathology as extranodal NK/T cell lymphoma, nasal type (ENKTL) with LMP1 positive in tumor tissue; 2. R/R ENKTL (meets one of the following prerequisites) 1. Without remission or with progression after receiving second-line or higher-line chemotherapy/chemotherapy + radiotherapy; 2. Primary drug resistance; 3. With recurrence after receiving autologous/allogeneic hematopoietic stem cell transplantation; 3. According to 2014 Lugano standard, there should be at least one evaluable tumor lesion. Only applicable to the inclusion criteria for LMP1-positive HL: 1. According to the 2016 WHO classification criteria for lymphocytic tumors, subjects with Hodgkin lymphoma diagnosed by histopathology (HD) and LMP1 positive in tumor tissue; 2. R/R HD (meets one of the following prerequisites): 1. Without remission or with progression after receiving second-line or higher-line chemotherapy; 2. Primary resistance Drugs; 3. With recurrence after receiving autologous hematopoietic stem cell transplantation; 3. According to the Lugano 2014 standard, there should be at least one evaluable tumor lesion; Only applicable to the inclusion criteria for LMP1-positive PTLD: 1. Only PTLD after hematopoietic stem cell transplantation; 2. According to the 2016 WHO classification criteria for lymphocytic tumors, subjects with PTLD diagnosed by histopathology and LMP1 positive in tumor tissue; 3. Excluding PTLD of early-stage 4. R/R PTLD (meets one of the following prerequisites): 1. Without remission or with progression after receiving rituximab-based standard treatment; 2. Primary drug resistance; 5. According to the Lugano 2014 standard, there should be at least one evaluable tumor lesion
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 LMP1 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 LMP1 targeted CAR T-cells infusion | Incidence of treatment-emergent adverse events \[Safety and Tolerability\] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CAEBV, Overall survival (OS) | Up to 2 years after LMP1 CAR-T cells infusion | From the first infusion of LMP1 CAR-T cells to death or the last visit |
| CAEBV, Relapse rate(RR) | At Month 6, 12, 18 and 24 | From the first remission after LMP1 CAR-T cells to relapse or the last visit |
| CAEBV, Event-free survival (EFS) | Up to 2 years after LMP1 CAR-T cells infusion | From the first infusion of LMP1 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 |
| Hodgkin's lymphoma(HL), Extranodal NK/T cell lymphoma(ENKTL),Nasal type, Lymphoproliferative disease after hematopoietic stem cell transplantation, (post-HSCT PTLD),Overall response rate (ORR) | At Month 1, 3, 6, 12, 18 and 24 | Assessment of ORR (ORR = CR + PR) at Month 1, 3, 6, 12, 18 and 24 |
| HL, ENKTL, PTLD, OS | Up to 2 years after LMP1 CAR-T cells infusion | From the first infusion of LMP1 CAR-T cells to death or the last visit |
| Chronic active EB virus infection (CAEBV), Overall response rate (ORR) | At Month 1, 3, 6, 12, 18 and 24 | Assessment of ORR (ORR = CR + PR) at Month 1, 3, 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 |
| HL, ENKTL, PTLD, EFS | Up to 2 years after LMP3 CAR-T cells infusion | From the first infusion of LMP1 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 |
| CAEBV，Duration of remission（DOR） | Up to 2 years after LMP1 CAR-T cells infusion | From the first remission after LMP1 CAR-T cells to relapse, death or the last visit |
Countries
China
Contacts
Primary ContactHe Huang, PhD
Backup ContactYongxian Hu, PhD
Outcome results
None listed