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

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

• 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.

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

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