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

NCT06716164 | Recruiting Early Phase 1

• 1 other identifier: Meta10-19-006
• 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 B-cell Non-Hodgkin lymphoma

Conditions

Non-hodgkin Lymphoma,B Cell

Keywords

Meta10-19; CAR-T Cells Therapy; B-cell Non-hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• MTD

  Determine the Maximal Tolerable Dose(MTD).

  MTD will be determined based on DLTs observed during the first 35 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 or donors 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: 19 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects or guardians must sign an informed consent form approved by the Ethics Committee in person before commencing any screening process;
• Age \> 18 years old, ≤ 70 years old, male or female;
• Diagnosis of relapsed/refractory (R/R) indolent B-cell lymphoma, and/or R/R diffuse large B-cell lymphoma (DLBCL). Refractory diseases are defined as one of the following：
• Patients with relapsed or refractory B-cell lymphoma treated with one standard treatment regimen and one salvage regimen treated with rituximab or another CD20 antibody drug and at least two treatment regiments appropriate for their disease, one of which should include anthracyclines;
• After treatment with these regimens, patients maintain SD (SD duration ≤ 12 months) or still progress；
• Recurrence after autologous hematopoietic stem cell transplantation, or recurrence of allogeneic HSCT, or inability to accept HSCT for various reasons；
• Patients with double-strike or triple-strike B-cell lymphoma who did not respond to second-line therapy；
• 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);
• If the subject has progressed or relapsed after prior CD19 CAR-T cell therapy, the planned apheresis phase should be at least 1 month after that, or the subject has been treated with other biologics, but is in the washout period;
• At least one measurable lesion at baseline, according to the Preliminary Assessment, staging and Response Assessment recommendations for Hodgkin's and non-Hodgkin's lymphoma (2014 edition);
• Expected survival time greater than 12 weeks;
• ECOG score 0-1 (subjects with central nervous system diseases caused by leukemia or lymphoma need to be determined by the investigator);
• Organ function：
• Complete blood count (CBC) test \[the following criteria should be met within 24 hours prior to apheresis, and supportive treatment such as transfusion, platelet transfusion, cell growth factor (except recombinant erythropoietin) should be avoided within 7 days prior to detection\]
• Lymphocyte count ≥ 0.5×109/L (except for those receiving bridging chemotherapy);

You may not qualify if:

• Patients with present or history of central nervous system diseases not associated with leukemia or lymphoma， 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);
• History of unstable angina and/or myocardial infarction within 6 months prior to signing the informed consent; History of uncontrolled thrombotic events, major bleeding, or deep venous thrombosis (DVT) within 12 months prior to signing the informed consent;
• 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);
• History of QT interval prolongation or severe cardiac disease;
• Before signing the informed consent form, the ADA (FMC63) test was significantly positive (the test result was weakly positive, and it was necessary to discuss with the investigator whether to rule it out);
• Other conditions that the investigator considered should not be enrolled in this clinical study.

Sponsors & Collaborators

• Zhejiang University: lead
• Leman Biotech Co., Ltd.: collaborator

Study Sites (1)

The first affiliated hospital of medical college of zhejiang university

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

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

Mingming Zhang

CONTACT

86-13656674208; mingmingzhang@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: November 29, 2024
• First Posted: December 4, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): April 5, 2027
• Last Updated: December 4, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)