CD19 CAR T-Cell Therapy for R/R Non-Hodgkin Lymphoma and Acute Lymphoblastic Leukemia

NCT ID: NCT06027957

Last Updated: 2025-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-02
• Study Completion Date: 2025-07-31

Brief Summary

• Brief Summary: Cluster of differentiation 19 (CD19) is expressed on B cells. CD19+ tumor cells in patients with non-Hodgkin lymphoma and acute lymphoblastic leukemia can be targeted using T cells expressing CD19-specific chimeric antigen receptor (CAR).
• Objective: This study aims to evaluate the safety and efficacy of single-dose anti-CD19 CAR T-cell therapy in the treatment of relapsed/refractory CD19+ non-Hodgkin lymphoma and acute lymphoblastic leukemia.
• Eligibility: People aged 1 to 60 years with relapsed/refractory CD19+ non-Hodgkin lymphoma and acute lymphoblastic leukemia.
• Design: Phase 1 clinical trial, uncontrolled, single dose of CD19 CAR T-cells.

Detailed Description

Objectives:

• Evaluate the frequency and severity of adverse events and serious adverse events (AEs/SAEs) of the therapy.
• Evaluate the response rate after CD19 CAR T-cell infusion according to the following criteria:

• Proportion of patients with complete response and partial response after CD19 CAR T-cell infusion
• Progression-free survival (PFS) after infusion of CD19 CAR T-cells
• Event-free survival (EFS) after infusion of CD19 CAR T-cells
• Overall survival (OS) after infusion of CD19 CAR T-cells

Conditions

B-Cell Non Hodgkin Lymphoma; B-Cell Acute Lymphoblastic Leukemia

Study Design

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

Study Groups

Treatment Regimen

• Experimental: Treatment Regimen.
• Leukapheresis to collect white blood cells using Spectra Optia Apheresis system.
• T cells selection, transduction, and CAR T-cell manufacturing using CliniMACS Prodigy. During this process, T cells will be genetically modified to express CD19 CAR.
• Lymphodepleting chemotherapy conditioning regimen for 3 days.
• CAR T-cells targeting CD19 will be infused intravenously at a dose between 1 and 2x10e6 cells/kg for 15-30 minutes.
• Following the T-cell infusion, patients will stay in the clinic for approximately 21-28 days to monitor toxicity.
• Outpatient follow-up will take place after 1 month, 3 months, and 6 months after infusion.

Group Type: EXPERIMENTAL

anti-CD19 CAR T-cells

Intervention Type: BIOLOGICAL

For Biological: CD19 CAR T-cells

• Dose: 1-2.10e6 cells/kg of weight
• Route: intravenous infusion

For Chemotherapy Drug:

• Fludarabine (30 mg/m2/day) given intravenously (IV) on day -5 to -3.
• Cyclophosphamide 500 mg/m2/day for NHL and 250 mg/m2/day for ALL given IV from day -5 to -3.
• Mesna 500 mg/m2/day for NHL and 250 mg/m2/day for ALL, divided in three infusions: one day before the cyclophosphamide infusion, and 4 and 8 hours after.

Interventions

anti-CD19 CAR T-cells

For Biological: CD19 CAR T-cells

• Dose: 1-2.10e6 cells/kg of weight
• Route: intravenous infusion

For Chemotherapy Drug:

• Fludarabine (30 mg/m2/day) given intravenously (IV) on day -5 to -3.
• Cyclophosphamide 500 mg/m2/day for NHL and 250 mg/m2/day for ALL given IV from day -5 to -3.
• Mesna 500 mg/m2/day for NHL and 250 mg/m2/day for ALL, divided in three infusions: one day before the cyclophosphamide infusion, and 4 and 8 hours after.

Intervention Type: BIOLOGICAL

Other Intervention Names

Chemotherapy Drug

Eligibility Criteria

Inclusion Criteria

• B-cell acute lymphoblastic leukemia: refractory to two cycles of chemotherapy, relapsed after chemotherapy, or hematopoietic stem cell transplantation.
• B-cell non-Hodgkin lymphoma: refractory to two lines of chemotherapy, relapsed after chemotherapy, or hematopoietic stem cell transplantation.
• Age: From 1 to 60 years old (both males and females)
• Adequate organ functions:

• Serum creatinine ≤ 1.5 x ULN or eGFR ≥ 60 mL/min/1.73 m2
• ALT and AST ≤ 5 x ULN; Bilirubin ≤ 2.0 mg/dl
• No chronic lung diseases, such as obstructive pulmonary disease or bronchial asthma, required continuous medications without respiratory failure (SpO2 oxygen saturation > 92% at room temperature).
• No arrhythmia, no intracardiac thrombus or vascular wall, no heart failure, LVEF ≥ 45%
• Blood test:

• Absolute neutrophil count (ANC) ≥ 1,000/mm3 (1 G/l) without filgrastim
• Absolute lymphocyte count ≥ 100/mm3 (0.1 G/l)
• Absolute platelet count ≥ 75,000/mm3 (75 G/l)
• Hemoglobin ≥ 8.0 g/dl
• Positive for CD19 measured by immunohistochemistry or flow cytometry.
• Agree to participate in the study
• Agree to use safe methods of contraception for female patients.

Exclusion Criteria

• Involved central nervous system invasion at the time of screening.
• Medical history of veno-occlusive disease (VOD).
• Required acute treatment due to tumors such as intestinal obstructions, vascular compression, or respiratory failure.
• Having active hemolytic anemia.
• Diagnosed with primary immunodeficiency.
• Medical history of autoimmune neurological diseases or neuromyelitis.
• Receiving immunosuppressive medication, except for ≤ 30 mg prednisolone or equivalent at the time of CAR-T-cell transfusion.
• Having acute, progressive, or chronic graft-versus-host disease (GvHD).
• Having active infectious diseases determined by clinical, imaging, or other laboratory tests (blood culture, PCR, etc.)
• Patients who are critically ill or at risk of premature death characterized by:

• Acute liver failure requiring dialysis
• Heart failure requiring vasopressors
• Systemic infection unresponsive to antibiotics
• ECOG performance status ≥ 3 points at the time of screening
• Having other severe concomitant diseases (e.g., uncontrolled arterial hypertension, heart failure NYHA III-IV).
• Unstable angina within 3 months prior to screening.
• Any previous or concurrent malignancy was not B-cell lymphoma or B-ALL.
• Medical history of clinically relevant central nervous system disease, such as epilepsy, convulsions, paralysis, aphasia, uncontrolled cerebrovascular disease, traumatic brain injury, and Parkinson's disease.
• Intolerance to excipients from cellular products.
• Pregnant women or those who expect to be pregnant or reastfeeding.
• Other diseases or other conditions and circumstances that, according to the investigator's assessment, make it difficult to ensure compliance with study treatment.
• Participation in another clinical trial at the time of screening

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Hematology and Blood Transfusion, Vietnam

OTHER

Sponsor Role: collaborator

Vinmec Research Institute of Stem Cell and Gene Technology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thanh Liem Nguyen, PhD

Role: PRINCIPAL_INVESTIGATOR

Vinmec Research Institute of Stem Cell and Gene Technology

Locations

Vinmec Research Institute of Stem Cell and Gene Technology

Hanoi, Hanoi, Vietnam

Countries

Vietnam

Other Identifiers

ISC19.26

Identifier Type: -

Identifier Source: org_study_id