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

NCT05747157 | Unknown Early Phase 1

• 1 other identifier: Meta10-19-002
• 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 B-cell Acute Lymphoblastic Leukemia

Conditions

B-cell Acute Lymphoblastic Leukemia

Keywords

Meta10-19; CAR-T Cells Therapy; r/r B-ALL

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: 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；
• Patients with relapsed and refractory B-cell Acute Lymphoblastic Leukemia.
• Definition of relapsed or refractory B-ALL (meeting one of the following conditions):
• or more relapses;
• Bone marrow relapsed after allo-HSCT and prepared to infuse Meta10-19 more than 6 months after allo-HSCT ;
• CR not achieved after standardized chemotherapy;
• Philadelphia-chromosome-positive (Ph+) patients who are ineffective or intolerant to first- and second-generation tyrosine kinase inhibitor (TKI) treatments, or who have contraindications to tyrosine kinase inhibitors;
• The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is ≥ 5%
• CD19 expression was positive by biopsy or flow cytometry (accept the results of this peripheral blood mononuclear cells collection or previous Class A tertiary hospital before this peripheral blood collection);
• Expected survival time greater than 12 weeks
• The baseline ECOG score was 0 or 1；
• Organ function：
• Kidney function:
• Serum creatinine ≤1.5 times ULN, or； The glomerular filtration rate (eGFR) estimated by MDRD formula was ≥60m/min/1.73m2；\[eGFR=186×（age）-0.203×SCr-1.154（mg/dl），for females, the result was ×0.742\]；
• Liver function： 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 isolated extramedullary relapse;
• Patients with confirmed diagnosis of Burkitt's lymphoma/ leukemia;
• Patients who had received prophylaxis for CNS leukemia within 1 week prior to Meta10-19 infusion;
• 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 (allo-HSCT) within 6 months prior to Meta10-19 infusion;
• 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。

Sponsors & Collaborators

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

Study Sites (1)

Anhui Provincial Hospital

Hefei, Anhui, China

RECRUITING

Related Publications (1)

• Xu Q, Guo Y, Gao M, Xue L, Xu H, Li H, Zhang X, Liu C, Li Y, Chen Q, Ren J, Sathiyanadan K, Hu Y, Tang L, Huang H, Wang X. IL-10-expressing, anti-CD19 CAR T cells for patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: an open-label, single-arm, phase 1 study. Lancet Haematol. 2025 Nov;12(11):e898-e907. doi: 10.1016/S2352-3026(25)00253-4. Epub 2025 Oct 16.

  PMID: 41110448 DERIVED

MeSH Terms

Conditions

Burkitt Lymphoma

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; 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: February 17, 2023
• First Posted: February 28, 2023
• Study Start: February 15, 2023
• Primary Completion: February 1, 2025
• Study Completion: May 15, 2025
• Last Updated: November 21, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)