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

NCT06393335 | Recruiting Early Phase 1

• 1 other identifier: Meta10-19-005
• Study Type: interventional
• Target: 36
• 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; 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: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age range: 6 months to 18 years old, inclusive, for both males and females.
• The patient or their guardian voluntarily signed the informed consent.
• Patients with relapsed or refractory CD19-positive B cell hematological malignancies:
• Relapsed or refractory B-ALL (meeting one of the following conditions):
• Patients who relapse within 30 months after the initial remission, with \>5% primordial cells (lymphoblast and prolymphocyte) in bone marrow morphology, confirmed by flow cytometry.
• Patients who relapse 30 months after the initial remission and fail to achieve complete remission or show poor response to early treatment after one course of standardized induction therapy.
• Patients who relapse after allogeneic hematopoietic stem cell transplantation (HSCT) and must undergo screening 3 months post-HSCT .
• Patients who do not achieve CR after standardized chemotherapy, or have \>1% minimal residual disease (MRD) in bone marrow after 3 months of chemotherapy.
• Philadelphia-chromosome-positive (Ph+) patients who do not achieve CR or relapse after being treated with at least two tyrosine kinase inhibitors (TKI).
• Patients who are not suitable candidates for allogeneic hematopoietic stem cell transplantation.
• Relapsed or refractory CD19+ B-NHL (meeting one of the following conditions):
• Patients who have been treated with CD20 antibodies (such as rituximab) and at least two chemotherapy regiments, one of which should include anthracyclines.
• After these treatments, patients experienced stable disease (SD) (with SD duration ≤12 months) or disease progression.
• Patients who relapse after auto/allo-HSCT, or are not eligible for HSCT.
• Patients with double-hit and triple-hit lymphoma who do not respond to second-line treatment.

You may not qualify if:

• Patients with a history of central nervous system (CNS) diseases other than CNS leukemia, such as seizures disorders, 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 have participated in other clinical trials within 30 days prior to enrollment.
• Patients with active hepatitis B (defined as positive for hepatitis B surface antigen or hepatitis B core antibody, with concomitant hepatitis B virus DNA level \> 1000 copies/ml) or hepatitis C (positive for HCV RNA).
• Patients who are positive for HIV antibodies or treponema pallidum antibodies.
• 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 may be eligible for enrollment under the following conditions:
• 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.
• Patients with active neuroautoimmune or inflammatory conditions (e.g., Guillian-Barre syndrome, amyotrophic lateral sclerosis).
• Patients with other conditions deemed unsuitable for enrollment in this clinical study by the investigator.

Sponsors & Collaborators

• The Children's Hospital of Zhejiang University School of Medicine: lead
• Leman Biotech Co., Ltd.: collaborator

Study Sites (1)

Children's Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 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

Xiaojun Xu, PhD

CONTACT

86- 13858067554; xuxiaojun@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 28, 2024
• First Posted: May 1, 2024
• Study Start: May 15, 2024
• Primary Completion: March 1, 2026
• Study Completion: March 15, 2026
• Last Updated: May 1, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)