CD19 CAR T-Cell Therapy for Relapsed B-Cell Cancers

Phase I Clinical Trial Evaluating the Safety and Efficacy of Point-of-care CAR-T-cell Therapy in the Treatment of Relapsed/Refractory CD19+ Non-Hodgkin Lymphoma and Acute Lymphoblastic Leukemia

This study is testing a new CAR T-cell therapy to see if it can help young people with relapsed B-cell cancers feel better and live longer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 1 Year to 60 Years
• Sex: All
• Sponsor: Vinmec Research Institute of Stem Cell and Gene Technology (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, CAR T, chimeric antigen receptor
• Locations: 1 site (Hanoi)
• Trial ID: NCT06027957 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of a single-dose anti-CD19 CAR T-cell therapy for patients with relapsed or refractory CD19+ non-Hodgkin lymphoma and acute lymphoblastic leukemia. The study aims to assess the frequency and severity of adverse events, as well as the response rates, progression-free survival, event-free survival, and overall survival following the infusion of CAR T-cells. Participants aged 1 to 60 years will receive the treatment, which targets CD19+ tumor cells using genetically modified T-cells. The trial is designed as a Phase 1, uncontrolled study to gather initial data on the therapy's effects.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 1 to 60 years with relapsed or refractory CD19+ non-Hodgkin lymphoma or acute lymphoblastic leukemia.

Not a fit: Patients with chronic lung diseases requiring continuous medications or those with significant cardiac issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with difficult-to-treat B-cell malignancies.

How similar studies have performed: Other studies using CAR T-cell therapy for similar conditions have shown promising results, indicating potential for success in this approach.

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

Where this trial is running

Hanoi

• Vinmec Research Institute of Stem Cell and Gene Technology — Hanoi, Vietnam (Recruiting)

Study contacts

• Principal investigator: Thanh Liem Nguyen, PhD — Vinmec Research Institute of Stem Cell and Gene Technology
• Study coordinator: Thanh Liem Nguyen, PhD

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