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

T-cell Acute Lymphoblastic Leukemia Clinical Trial

— BAH246  

Official title:

This is an Open, Single-arm, Clinical Study to Evaluate the Efficacy and Safety of Anti-CD7/CD5 CAR-T Cells in the Treatment of Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia (T-ALL), ETP-ALL, and Lymphoblastic Lymphoma (TLBL).

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06420076
• Other study ID #: ESBI202496
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: September 10, 2024
• Est. completion date: December 28, 2026

Study information

• Verified date: May 2024
• Source: Essen Biotech
• Contact: JAMAL ALKHAYER
• Phone: +97333799773
• Email: ceo[@]essen-biotech.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 28, 2026
• Est. primary completion date: December 10, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 90 Years

Eligibility

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).

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Leukemia, Prolymphocytic
• Leukemia, Prolymphocytic, T-Cell
• Leukemia, T-Cell
• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• T Cell Leukemia
• T Cell Lymphoma
• T-cell Acute Lymphoblastic Leukemia

Intervention

Biological:
• 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.

Locations

Country	Name	City	State
China	District one hospital	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Essen Biotech

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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