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

NCT06420076 | Recruiting Phase 1 DMC

• 1 other identifier: ESBI202496
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

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

Keywords

CAR-T; CD5; CD7; ETP-ALL

Outcome Measures

Primary Outcomes (2)

• The number and incidence of adverse events after CD7/CD5 CAR infusion.

  Evaluation of all possible adverse reactions, including the number, incidence, and severity of symptoms such as cytokine release syndromes and neurotoxicity within 3 months after CAR-T infusion

  28 days

• Disease response to CD7/CD5 CAR T cells

  The disease response to CD7/CD5 CAR T cells is evaluated by bone marrow biopsy and aspirate within 1 year after CAR infusion. The proportion of subjects receiving CD7/CD5 CAR T infusion to 1) morphological remission (blasts \<5%): 2) flow cytometry analysis was blast negative, and 3) molecular biological remission (if applicable).

  1 year

Study Arms (1)

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

EXPERIMENTAL

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.

Biological: CD5/CD7 CAR-T

Interventions

CD5/CD7 CAR-T 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.

Also known as: EB-BH2026

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

Eligibility Criteria

• Age: 2 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Essen Biotech: lead

Study Sites (1)

District One Hospital

Beijing, Beijing Municipality, 086-373, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, T-Cell; Leukemia, T-Cell; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Prolymphocytic, T-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; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Prolymphocytic

Central Study Contacts

Rhoda M Smith, Phd

CONTACT

+12077706670; clinical-trials@essen-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open-label clinical trials are a category of clinical research where the masking is minimal or nonexistent. In such trials, both the participants and the researchers are fully aware of the treatment assignments, which means participants know the treatment they are receiving, and researchers are aware of each participant's treatment group.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients enrolled in this clinical trial will receive a carefully designed treatment regimen. Prior to the infusion of CD5 and CD7 CAR-T cells, participants will undergo preconditioning chemotherapy. This chemotherapy serves to create an optimal environment for CAR-T cell therapy to effectively target and eliminate malignant B cells. Following chemotherapy, participants will receive the infusion of CD5 and CD7 CAR-T cells.

Study Record Dates

• First Submitted: May 14, 2024
• First Posted: May 17, 2024
• Study Start: July 10, 2024
• Primary Completion: December 10, 2025
• Study Completion (Estimated): December 28, 2026
• Last Updated: November 12, 2024

Record last verified: 2024-11

Locations

CN (1)