B-Cell Acute Lymphoblastic Leukemia, B-Cell Non Hodgkin Lymphoma
Conditions
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
Interventions
BIOLOGICALanti-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.
Sponsors
National Institute of Hematology and Blood Transfusion, Vietnam
Vinmec Research Institute of Stem Cell and Gene Technology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of the frequency and severity of adverse events and serious adverse events (AEs/SAEs) of the therapy | 6 months | The incidence of adverse events (AEs) and serious adverse events (SAEs) will be recorded and classified according to CTCAE v5 (grade 1-5). CRS and ICANs will be classified using the ASTCT criteria (grade 1-5). These parameters will be used to assess the safety of the therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with complete response and partial response after CD19 CAR T-cell infusion (%) | Day 30 and day 90 after CAR-T infusion for B-ALL; day 90 after CAR-T infusion for NHL | Patients with B-ALL will receive bone marrow biopsy assessed on day 30 and day 90 to check blast frequency and MRD. The response will be classified according to NCCN guidelines. Patients with NHL will be examined PET-CT or CT on day 90. The response will be classified according to Cheson guidelines. |
| Progression-free survival (PFS) (months) | 6 months | PFS is defined as the time from CAR T-cell infusion, until disease progression or death from any cause. Progression is defined as an increase of tumor load, the development of new lesions. |
| Event-free survival (EFS) (months) | 6 months | EFS is defined as time to treatment failure (including complete remission with incomplete hematologic or platelet recovery), relapse from complete remission, or death from any cause. |
| Overall survival (OS) (months) | 6 months | EFS is defined as time to death |
Countries
Vietnam
Outcome results
None listed