Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of Relapsed and/or Refractory CD19-positive B Cell Hematological Malignancies Clinical Research

NCT06277011 | Recruiting Early Phase 1

• 1 other identifier: Meta10-19-004
• 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 CD19-positive B cell Hematological Malignancies

Conditions

Acute Lymphoblastic Leukemia; Non-hodgkin Lymphoma

Keywords

Meta10-19 CAR-T Cells Therapy; r/r CD19-positive B cell Hematological Malignancies

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)

• Concentration of CAR-T cells

  Up to 12 months after CAR-T treatment

• Pharmacodynamics of CAR-T cells

  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: 3 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient or his/her guardian voluntarily signed the informed consent.
• Meeting one of the following conditions:
• Patients with relapsed or refractory B-cell lymphoma who have received CD20 antibodies (such as rituximab) and at least two chemotherapy treatments, one of which should include anthracyclines. After these regimens, patients maintained SD (SD duration ≤12 months) or disease progression.
• Partial remission (PR) or minimal residual lesions after two chemotherapy treatments.
• Recurrence after autologous hematopoietic stem cell transplantation.
• Extramedullary recurrence or residual leukemia cells ≥ 0.01% in bone marrow after allogeneic hematopoietic stem cell transplantation.
• Patients with relapsed or refractory B-ALL who not suitable for hematopoietic stem cell transplantation.
• CD19 expression was positive by immunohistochemistry or flow cytometry (\>30%)，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.
• Patients with proper organ function:
• Kidney function is defined as:
• Serum creatinine ≤1.5 times ULN, or; The glomerular filtration rate (eGFR) estimated by MDRD formula was ≥60m/ min/1.73m2.
• Liver function is defined as: ALT≤5 times ULN, and; Patients with total bilirubin ≤2.0mg/dl, except those with Gilbert-Meulengracht syndrome. Patients with Gilbert-Meulengracht syndrome with total bilirubin ≤3.0 times ULN and direct bilirubin ≤1.5 times ULN were included.

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 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.
• B-ALL patients meeting one of the following conditions:

Sponsors & Collaborators

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

Study Sites (1)

Anhui Provincial Hospital

Hefei, Anhui, 518000, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma

Central Study Contacts

Xingbing Wang, PhD

CONTACT

+8613856007984; 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: February 18, 2024
• First Posted: February 26, 2024
• Study Start: February 10, 2023
• Primary Completion: February 1, 2025
• Study Completion: May 15, 2025
• Last Updated: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)