Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of r/r DLBCL Clinical Research

NCT05715606 | Unknown Early Phase 1

• 1 other identifier: Meta10-19-001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

A Study of Metabolically Armed CD19 CAR-T Cells Therapy for Patients With Relapsed and/or Refractory Diffuse Large B-Cell Lymphoma

Conditions

Diffuse Large B-cell Lymphoma

Keywords

Meta10-19; CAR-T Cells Therapy; r/r DLBCL

Outcome Measures

Primary Outcomes (2)

• MTD

  Determine the Maximal Tolerable Dose(MTD)

  MTD will be determined based on DLTs observed during the first 28 days of study treatment.

• Objective response rate (ORR)

  Measure Tumor response rate (including CR and PR) .

  Within 3 months following infusion of Meta10-19

Secondary Outcomes (2)

• Pharmacokinetics

  Up to 12 months after CAR-T treatment

• Pharmacodynamics

  Up to 28 days after infusion

Study Arms (1)

Administration of Metabolically Armed CD19 CAR-T cells

EXPERIMENTAL

Patients undergo leukapheresis. Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CAR-T cells infusion. A dose of metabolically armed CD19 CAR-T cells will be infused on day 0.

Drug: Metabolically Armed CD19 CAR-T cells

Interventions

Metabolically Armed CD19 CAR-T cells DRUG

Each subject receive metabolically armed CD19 CAR-T cells by intravenous infusion

Also known as: Meta10-19

Administration of Metabolically Armed CD19 CAR-T cells

Eligibility Criteria

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

You may qualify if:

• The patient or his/her guardian voluntarily signed the informed consent;
• Adult Patients with relapsed and refractory diffuse large B-cell lymphoma (Primary mediastinal large B-cell lymphoma and transformed follicular lymphoma are included)
• Definition of refractory:
• No response to the last treatment, including:
• The best response to the last treatment was PD, or ; The best response to the last treatment was SD and the duration was not more than 6 months after the last dose.
• Not suitable for autologous hematopoietic stem cell transplantation (ASCT), or ASCT refractory, including:
• Disease progression or recurrence within 12 months or less (recurrence must be confirmed by biopsy) after ASCT treatment, or; Patients accept remedial treatment after ASCT must have no response or relapse after the last treatment.
• Patients who had previously received ≥2 lines therapy including at least:
• A chemotherapy regimen containing anthracyclines；
• For patients with transformed DLBCL from follicular lymphoma, they must have previously received chemotherapy for follicular lymphoma and have refractory disease after transformation to DLBCL.
• CD19 expression was positive by immunohistochemistry or flow cytometry (accept the results of this peripheral blood mononuclear cells or previous report from a Class A tertiary hospital before peripheral blood collection)
• At least one measurable lesion at baseline, according to the initial assessment, staging and Response Assessment recommendations for Hodgkin's and non-Hodgkin's lymphoma (2014 edition)
• Expected survival time greater than 12 weeks
• The baseline ECOG score was 0 or 1
• organ function：

You may not qualify if:

• Patients with present or history of central nervous system diseases such as seizures disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
• Patients with history of allogeneic hematopoietic stem cell transplantation
• Patients who had received chemotherapy other than preconditioning chemotherapy within 2 weeks prior to Meta10-19 infusion
• Patients who participated in other clinical trials within 30 days prior to enrollment
• Patients with active hepatitis B (defined as hepatitis B surface antigen positive or hepatitis B core antibody positive, concomitant hepatitis B virus DNA level \> 1000 copies/ml) or hepatitis C (HCV RNA positive)
• Patients with HIV antibody positive or treponema pallidum antibody positive
• Patients with uncontrolled acute life-threatening bacterial, viral or fungal infections (e.g. positive blood cultures ≤72 hours before Meta10-19 infusion)
• Patients with unstable angina pectoris and/or myocardial infarction within 6 months prior to enrollment
• Patients with history of other malignancies, but the following conditions can be enrollment:
• Adequately treated basal or squamous cell carcinoma (requiring adequate wound healing before signing informed consent);
• Carcinoma in situ (DCIS) of cervical or breast cancer, which has been treated therapeutically, has shown no signs of recurrence for at least 3 years prior to the signing of the informed consent；
• The primary malignancy has been completely resected and in complete remission for ≥5 years；
• Women who are pregnant or breastfeeding (pregnancy tests for women of childbearing age are positive)
• Patients with active neuroautoimmune or inflammatory conditions (e.g. Guillian-Barre syndrome, amyotrophic lateral sclerosis);
• Other conditions that the investigator considered should not be enrolled in this clinical study, such as poor compliance.

Sponsors & Collaborators

• Anhui Provincial Hospital: lead
• Leman Biotech Co., Ltd.: collaborator

Study Sites (1)

Anhui Provincial Hospital

Hefei, Anhui, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Xingbing Wang, PhD

CONTACT

86-13856007984; wangxingbing@ustc.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2022
• First Posted: February 8, 2023
• Study Start: February 10, 2023
• Primary Completion: February 1, 2025
• Study Completion: May 15, 2025
• Last Updated: July 5, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)