Study of alloCART-19 Cell Therapy in Pediatric Patients With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia
- Conditions
- ALL, Childhood B-Cell
- Interventions
- Registration Number
- NCT04173988
- Lead Sponsor
- Children's Hospital of Fudan University
- Brief Summary
The purpose of this study is to evaluate the safety and tolerability of CD19-Directed Allogeneic Chimeric Antigen Receptor T- cell (alloCART-19)therapy in pediatric patients with relapsed/refractory acute lymphoblastic leukemia（ALL）.
- Detailed Description
This is a single center, open label, single arm, dose escalation study to explore the safety, tolerability, and pharmacokinetic / pharmacodynamic profile of CD19-Directed Allogeneic Chimeric Antigen Receptor T- cell (alloCART-19) in pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia. The study will also assess the preliminary efficacy of CD19-Directed Allogeneic Chimeric Antigen Receptor T- cell (alloCART-19). For this exploratory clinical trial, approximately 3-6 patients will be enrolled. During dose escalation, at least one evaluable patient will be enrolled at each dose level. Once DLT is reached, 1 to 3 additional patients will be enrolled at the dose level below DLT, which has been tested and determined to be safe in the trial, to evaluate the optimal safe and therapeutic dose to be approved by the investigator and sponsor.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 6
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description alloCART-19 Fludarabine For the very first patient, the initial dose could be administered via one or three intravenous infusions within 1 to 5 days. Starting from the second patient, the investigator will decide whether to use single or multiple alloCART-19 infusions, based on the treatment experience at previous dose level(s) and the patient's baseline disease burdens. A lymphodepletion conditioning with cyclophosphamide and fludarabine will be conducted before alloCART-19 infusion. alloCART-19 alloCART-19 For the very first patient, the initial dose could be administered via one or three intravenous infusions within 1 to 5 days. Starting from the second patient, the investigator will decide whether to use single or multiple alloCART-19 infusions, based on the treatment experience at previous dose level(s) and the patient's baseline disease burdens. A lymphodepletion conditioning with cyclophosphamide and fludarabine will be conducted before alloCART-19 infusion. alloCART-19 Cyclophosphamide For the very first patient, the initial dose could be administered via one or three intravenous infusions within 1 to 5 days. Starting from the second patient, the investigator will decide whether to use single or multiple alloCART-19 infusions, based on the treatment experience at previous dose level(s) and the patient's baseline disease burdens. A lymphodepletion conditioning with cyclophosphamide and fludarabine will be conducted before alloCART-19 infusion.
- Primary Outcome Measures
Name Time Method Dose Limiting Toxicity Day 28 after the first alloCART-19 infusion Dose Limiting Toxicity (DLT) is defined as patients with the adverse event (AE) or laboratory abnormality per Lee DW and Locke FL standards and management guideline, and should be possibly related to alloCART-19 cell therapy, and should be unrelated to the disease itself, disease progression, concomitant diseases or concomitant medication. DLT will be analyzed as categorical variable，coded as 1 for DLT occur, 0 for no DLT.
- Secondary Outcome Measures
Name Time Method The occurrence of adverse events After the first alloCART-19 infusion for 2 year The adverse events (AE) is a composite variable including liver and kidney function damage, nausea, vomiting, arrhythmia and dyspnea. The variable would be coded as 1 if any of these events occurs after the first alloCART-19 infusion while 0 for none . These adverse events would be measured by assessment scale method according to NCI CTC AE v5.0 classification standard.
Objective Response Rate Day 28 and 3 months after the first alloCART-19 infusion Objective Response Rate（ORR）is defined as the proportion of patients whose tumor volume shrank to a predetermined value and the minimum time limit required.
ORR = complete remission (CR) + incomplete complete remission (CRi)Best Overall Response Day 28 and 3 months after the first alloCART-19 infusion Best Overall Response（BOR）at 28 days and 3 months after drug infusion was evaluated to preliminarily evaluate the optimal efficacy of alloCART-19 infusion in patients.
Trial Locations
- Locations (1)
Children's Hospital of Fudan University
🇨🇳Shanghai, Minhang, China