Sequential CAR-T Cells Therapy for CD5/CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD5/CD7-Specific CAR-T Cells

NCT ID: NCT06420076

Last Updated: 2024-11-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-10
• Study Completion Date: 2026-12-28

Brief Summary

Chimeric antigen receptor (CAR)-modified T cells targeted against CD19 have demonstrated unprecedented successes in treating patients with hematopoietic and lymphoid malignancies. Besides CD19, many other molecules such as CD22, CD30,BCMA,CD123, etc. may be the potential to develop the corresponding CAR-T cells to treat patients whose tumors express those markers. In this study, investigators will evaluate the safety and efficacy of Sequential CAR-T Cells Targeting CD5/CD7 in patients with patients with relapsed or refractory T-ALL/LBL/ETP-ALL. The primary goal is safety assessment including cytokine storm response and any other adverse effects. In addition, disease status after treatment will also be evaluated.

Detailed Description

Acute lymphoblast leukemia (T-ALL) is a neoplastic lymphoid leukemia characterized by the proliferation of immature precursor T cells. The combined chemotherapy has significantly improved the prognosis of T-acute lymphoblast leukemia/lymphoma. However, once the disease appears to be relapsed/refractory, there are limited treatment options, and the overall prognosis is extremely poor. Therefore, exploring safe and effective treatments is a critical unmet medical need. The patients will receive Sequential CAR-T Cells Targeting CD5/CD7 to examine the safety and, possibly the efficacy of CD5 CAR T-Cells in CD5+ CD7+ relapsed or refractory acute leukemia.

Conditions

T Cell Lymphoma; T Cell Leukemia; T-cell Acute Lymphoblastic Leukemia; T-Cell Lymphoma of CNS; T Cell Prolymphocytic Leukemia; T Cell Childhood ALL

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sequential CAR-T Cells Targeting (CD5/CD7 CAR T cells, chemotherapy)

Patients will be administered fludarabine phosphate intravenously (IV) over a 30-minute period on days -4 to -2. Additionally, cyclophosphamide will be administered intravenously (IV) over 60 minutes on day -2. Subsequently, patients will receive CD5/CD7 CAR T cells intravenously (IV) over a duration of 10-20 minutes on day 0. Patients who exhibit positive responses to the initial dose of CD5/CD7 CAR T cells, do not experience unacceptable side effects, and have a sufficient quantity of cells available may be eligible to receive 2 or 3 additional doses of CD5/CD7 CAR T cells.

Group Type: EXPERIMENTAL

CD5/CD7 CAR-T

Intervention Type: BIOLOGICAL

The intervention in this clinical trial involves a novel approach using CD5/CD7 Chimeric Antigen Receptor T (CAR T) cells combined with chemotherapy. The goal is to assess safety and efficacy in patients with specific hematologic malignancies.

Treatment Regimen:

Patients in the trial will undergo the following regimen:

Fludarabine Phosphate (Days -4 to -2): IV administration of fludarabine phosphate over 30 minutes on days -4 to -2. It's part of the preparatory regimen to enhance the body's response to CAR T-cell therapy.

Cyclophosphamide (Day -2): IV cyclophosphamide over 60 minutes on day -2.

CD5/CD7 Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, CD5/CD7 CAR T cells, over 10-20 minutes on day 0.

Additional Doses: Eligible patients responding well to the initial CD5/CD7 CAR-T cell infusion without unacceptable side effects and sufficient CAR-T cell availability may receive 2 or 3 additional doses.

Interventions

CD5/CD7 CAR-T

The intervention in this clinical trial involves a novel approach using CD5/CD7 Chimeric Antigen Receptor T (CAR T) cells combined with chemotherapy. The goal is to assess safety and efficacy in patients with specific hematologic malignancies.

Treatment Regimen:

Patients in the trial will undergo the following regimen:

Fludarabine Phosphate (Days -4 to -2): IV administration of fludarabine phosphate over 30 minutes on days -4 to -2. It's part of the preparatory regimen to enhance the body's response to CAR T-cell therapy.

Cyclophosphamide (Day -2): IV cyclophosphamide over 60 minutes on day -2.

CD5/CD7 Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, CD5/CD7 CAR T cells, over 10-20 minutes on day 0.

Additional Doses: Eligible patients responding well to the initial CD5/CD7 CAR-T cell infusion without unacceptable side effects and sufficient CAR-T cell availability may receive 2 or 3 additional doses.

Intervention Type: BIOLOGICAL

Other Intervention Names

EB-BH2026

Eligibility Criteria

Inclusion Criteria

• Signed written informed consent; Patients volunteer to participate in the clinical trial;
• Diagnosis is mainly based on the World Health Organization (WHO) 2008;
• Complete remission cannot be achieved after induction therapy; recurrence occurs after completion remission; the burden of leukemic blasts in the peripheral blood or bone marrow is greater than 5%;
• Leukemic blast cells express CD7/CD5 (CD7 OR CD5 positive by flow cytometry or immunohistochemistry ≥70%);
• The expected survival period is greater than 12 weeks;
• ECOG score ≤2;
• Age 2-60 years old;
• HGB≥70g/L (can be transfused);
• Total bilirubin does not exceed 3 times the upper limit of normal value, and AST and ALT do not exceed 5 times the upper limit of normal value.

Exclusion Criteria

• Patients declining to consent for treatment
• Prior solid organ transplantation
• One of the following cardiac issues: atrial fibrillation; myocardial infarction within the past 12 months; prolonged QT syndrome or secondary QT prolongation; clinically significant pericardial effusion; cardiac insufficiency NYHA (New York Heart Association) III or IV;
• History of severe pulmonary dysfunction diseases;
• Severe infection or persistent infection cannot be effectively controlled;
• Severe autoimmune disease or congenital immunodeficiency;
• Active hepatitis;
• Human immunodeficiency virus (HIV) infection;
• Clinically significant viral infections, or uncontrollable viral reactivation, including EBV (Epstein-Barr virus).

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Essen Biotech

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

District One Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Rhoda M Smith, Phd

Role: CONTACT

clinical-trials@essen-biotech.com

+12077706670

Facility Contacts

SAMI XI, dr

Role: primary

SFM@districtonehospital.com

+14012275001

Other Identifiers

ESBI202496

Identifier Type: -

Identifier Source: org_study_id