Clinical trial NCT06027957: CD19 CAR T-Cell Therapy for R/R Non-Hodgkin Lymphoma and Acute Lymphoblastic Leukemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: B-Cell Non Hodgkin Lymphoma
B-Cell Acute Lymphoblastic Leukemia
Lead sponsor: Vinmec Research Institute of Stem Cell and Gene Technology
Sponsor class: OTHER
Collaborators: name: National Institute of Hematology and Blood Transfusion, Vietnam
First posted: 2023-09-07
Enrollment: 16
Sex: ALL
Minimum age (years): 1
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Assessment of the frequency and severity of adverse events and serious adverse events (AEs/SAEs) of the therapy
timeFrame: 6 months
Secondary outcomes:
measure: Proportion of patients with complete response and partial response after CD19 CAR T-cell infusion (%)
timeFrame: Day 30 and day 90 after CAR-T infusion for B-ALL; day 90 after CAR-T infusion for NHL
measure: Progression-free survival (PFS) (months)
timeFrame: 6 months
measure: Event-free survival (EFS) (months)
timeFrame: 6 months
measure: Overall survival (OS) (months)
timeFrame: 6 months
Other outcomes:
Locations:
city: Hanoi
country: Vietnam
facility: Vinmec Research Institute of Stem Cell and Gene Technology
Study officials:
affiliation: Vinmec Research Institute of Stem Cell and Gene Technology
name: Thanh Liem Nguyen, PhD
role: PRINCIPAL_INVESTIGATOR
References: