The purpose of this study is to learn more about newer methods of transplanting blood cells donated by a partially matched family member to children with high-risk CD19 positive leukemia ALL.
Primary Objective:
\- To assess the safety and feasibility of combining CD19-CAR(Mem) T cells after TCRαβ+/CD19 depleted haploidentical donor transplantation for pediatric patients with relapsed/refractory CD19+ B-cell malignancies.
Secondary Objectives:
* To estimate 1-year post-transplant overall survival, event-free survival, and GVHD-free relapse-free survival (GRFS). * To estimate cumulative incidence of engraftment, acute and chronic GVHD, and immune-related adverse events, including CRS and ICANS.
Age less than or equal to 21 years
High risk CD19+ B cell ALL in CR1 or CR2
Any CD19+ B-cell ALL in CR3 or subsequent
If prior CNS leukemia, it must be treated and in CNS CR
Has a suitable HLA-identical sibling or suitable 12/12 (HLA-A, B, C, DRB1, DQB1, and DPB1) HLA-matched unrelated donor available in an appropriate time frame
Any other active malignancy other than the one for which this HCT is indicated
Received a prior allogeneic HCT at any time
Pregnant, if female is of childbearing potential, negative test must be confirmed by serum or urine pregnancy test within 14 days prior to enrollment
Single group
Anti-Thymocyte Globulin (Rabbit)
DrugDays -10, -11, -12.
Cyclophosphamide
Drug60 mg/kg intravenous once daily on day -9.
Fludarabine
Drug30 mg/m2 intravenous once daily for \>10 kg, 1 mg/kg intravenous once daily for ≤10 kg on days -4, -5, -6, -7, -8.
Thiotepa
Drug5 mg/kg intravenous twice daily on day -3.
Mesna
DrugMesna is planned to be administered at 15 mg/kg/dose prior to cyclophosphamide and at approximately 3, 6, and 9 hours after the cyclophosphamide infusion, to give a 1:1 ratio of mesna:cyclophosphamide.
Melphalan
Drug70 mg/m2 intravenous once daily for \>10 kg, 2.3 mg/kg intravenous once daily for ≤10 kg on days -1, and -2.
Filgrastim
DrugG-CSF\* 10 mcg/kg/day SC days 0, -1, -2, -3, -4, -5.
CliniMACS System
DeviceThe mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest.
To assess the safety of combining CD19-CAR(Mem) T cells after TCRαβ+/CD19 depleted haploidentical donor transplantation for pediatric patients with relapsed/refractory CD19+ B-cell malignancies.
The primary analysis will compute the sample proportions and corresponding binomial exact 95% confidence intervals among evaluable patients for the following toxicities (separately for each toxicity) within 100 days post-HCT: 1) Severe aGVHD defined as Grade 3-4 aGVHD 2) Severe CRS defined as Grade 4 CRS that does not resolve to grade 3 or lower within 72 hours of onset 3) Severe ICANS defined as Grade 4 ICANS that does not resolve to grade 3 or lower within 72 hours of onset 4) TRM defined as death without prior relapse or disease progression within 100 days post-HCT 5) Other toxicity data will also be reported for a complete safety assessment of the study regimen.
To assess the feasibility of combining CD19-CAR(Mem) T cells after TCRαβ+/CD19 depleted haploidentical donor transplantation for pediatric patients with relapsed/refractory CD19+ B-cell malignancies.
this will be measured by the failure to receive CD19-CAR(Mem) T cells among patients who received HCT. The number of patients who fail to receive addback will be reported as the proportion who were unable to receive addback within 60 days post-HCT
To assess the feasibility of combining CD19-CAR(Mem) T cells after TCRαβ+/CD19 depleted haploidentical donor transplantation for pediatric patients with relapsed/refractory CD19+ B-cell malignancies.
This will be measured by the failure to receive CD19-CAR(Mem) T cells among patients who received HCT. The number of patients who fail to receive addback will be reported as the proportion who were unable to receive addback within 60 days post-HCT
Estimate 1-year post-transplant relapse free survival
This this will be estimated by the Kaplan-Meier method
Estimate cumulative incidence of neutrophil engraftment
This will be summarized by cumulative incidence functions estimated by the Kalbfleisch-Prentice method.
Estimate cumulative incidence of platelet engraftment
This will be summarized by cumulative incidence functions estimated by the Kalbfleisch-Prentice method.
Click on the lead sponsor to view all of their trials.
