LMP1 CAR-T for Patients With LMP1 Positive Infectious Diseases and Hematological Malignancies

NCT04657965 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: LMP1-001
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

A study of LMP1 CAR-T for patients with LMP1 positive infectious diseases and hematological malignancies

Conditions

Infectious Diseases; Hematological Malignancies

Keywords

Infectious diseases; Hematological Malignancies; CAR T-cell therapy; LMP1

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT)

  Adverse events assessed according to NCI-CTCAE v5.0 criteria

  Baseline up to 28 days after LMP1 targeted CAR T-cells infusion

• Incidence of treatment-emergent adverse events (TEAEs)

  Incidence of treatment-emergent adverse events \[Safety and Tolerability\]

  Up to 2 years after LMP1 targeted CAR T-cells infusion

Secondary Outcomes (12)

• Chronic active EB virus infection (CAEBV), Overall response rate (ORR)

  At Month 1, 3, 6, 12, 18 and 24

• CAEBV，Duration of remission（DOR）

  Up to 2 years after LMP1 CAR-T cells infusion

• CAEBV, Overall survival (OS)

  Up to 2 years after LMP1 CAR-T cells infusion

• CAEBV, Relapse rate(RR)

  At Month 6, 12, 18 and 24

• CAEBV, Event-free survival (EFS)

  Up to 2 years after LMP1 CAR-T cells infusion

Study Arms (1)

Administration of LMP1 CAR T-cells

EXPERIMENTAL

Each subject receive LMP1 CAR T-cells by intravenous infusion

Drug: LMP1 CAR T-cells

Interventions

LMP1 CAR T-cells DRUG

Each subject receive LMP1 CAR T-cells by intravenous infusion

Also known as: LMP1 CAR-T cells injection

Administration of LMP1 CAR T-cells

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• All CAEBV patients who have not achieved complete remission, including:
• 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;
• inactive phase: EBV-DNA level in PBMC is higher than 1×10\^2.5 copies/μg DNA, without symptoms and signs of active diseases;
• The disease has not yet progressed to hematopoietic lymphohistiocytosis (HLH);
• 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;
• R/R ENKTL (meets one of the following prerequisites)
• Without remission or with progression after receiving second-line or higher-line chemotherapy/chemotherapy + radiotherapy;
• Primary drug resistance;
• With recurrence after receiving autologous/allogeneic hematopoietic stem cell transplantation;
• According to 2014 Lugano standard, there should be at least one evaluable tumor lesion.
• According to the 2016 WHO classification criteria for lymphocytic tumors, subjects with Hodgkin lymphoma diagnosed by histopathology (HD) and LMP1 positive in tumor tissue;
• R/R HD (meets one of the following prerequisites):
• Without remission or with progression after receiving second-line or higher-line chemotherapy;
• Primary resistance Drugs;

You may not qualify if:

• History of craniocerebral trauma, conscious disturbance,epilepsy,cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
• Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
• Pregnant (or lactating) women;
• Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
• Active infection of hepatitis B virus or hepatitis C virus;
• Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving in haled steroids;
• Previously treated with any CAR-T cell product or other genetically modified T cell therapies;
• Creatinine\>2.5mg/dl, or ALT / AST \> 3 times of normal amounts, or bilirubin\>2.0 mg/dl;
• Other uncontrolled diseases that were not suitable for this trial;
• Patients with HIV infection;
• Any situations that the investigator believes may increase the risk ofpatients or interfere with the results of study

Sponsors & Collaborators

• Zhejiang University: lead
• Yake Biotechnology Ltd.: collaborator

Study Sites (1)

The First Affiliated Hospital，College of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

MeSH Terms

Conditions

Communicable Diseases; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

He Huang, PhD

CONTACT

86-13605714822; hehuangyu@126.com

Yongxian Hu, PhD

CONTACT

86-15957162012; huyongxian2000@aliyun.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: October 22, 2020
• First Posted: December 8, 2020
• Study Start: January 15, 2021
• Primary Completion: January 15, 2024
• Study Completion (Estimated): January 15, 2027
• Last Updated: December 8, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)