This single arm pilot phase I study with safety run-in is designed to estimate the safety and efficacy of a familial mismatched or haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using a novel graft modification technique (selective αβ-TCR and CD19 depletion).
≥ 1% for NCI SR ALL
≥ 0.01% for NCI HR ALL
TCF3-HLF t(17;19)
KMT2A rearranged infant ALL, < 6 months of age and presenting WBC of > 300,000 or poor steroid response (peripheral blasts >= 1000 /uL on day 8 of therapy
Available matched related donor. A patient with a matched unrelated donor is eligible if urgent transplantation is required. A prior unrelated donor search is not required for enrollment.
Active non-hematologic malignancy. History of other malignancy is acceptable as long as therapy has been complete and there is no evidence of disease.
Currently receiving any other investigational agents at the time of transplant.
Active CNS or extramedullary disease. History of CNS or extramedullary disease now in remission is acceptable.
Parallel
Ex Vivo T-cell receptor alpha-beta and CD19+ Depletion using CliniMACs Plus
DeviceOnce pheresed, the product will be washed to remove platelets and the cell concentration will be adjusted per laboratory and ClinicMACS technology recommendations. It is then labeled using the CliniMACS αβ-TCR Biotin Kit and CD19+ immunomagnetic microbeads. After labeling, the cells are washed to remove unbound microbeads. The partially processed product is loaded on the CliniMACS device where labeled cells are depleted and the negative fraction is eluted off the device. The negative fraction is centrifuged and volume reconstituted to obtain the final product
Safety as measured by the number of events occurring within the first 100 days post-transplant
-Events are death, disease recurrence or progression, and graft failure
Engraftment as measured by time to neutrophil count recovery
Time to neutrophil recovery is defined as the first of 3 measurements on different days when the patient has an absolute neutrophil count of \>500/μL after conditioning.
Engraftment as measured by time to platelet count recovery
Time to platelet recovery is defined as the first day of a minimum of 3 measurements on different days that the patient has achieved a platelet count \> 50,000/μL AND did not receive a platelet transfusion in the previous 7 days. The exception is the case in which a patient receives platelet transfusions specifically to achieve a higher platelet threshold to allow for an invasive procedure or protection if determined to be at elevated bleeding risk.
Donor cell chimerism as measured by short tandem repeat analysis
* Can use peripheral blood samples or bone marrow samples * The percent of donor-derived cells are sequentially followed.
Event free survival (EFS)
-Death, disease recurrence or progression, and graft failure are considered events
Overall survival (OS)
Death by any cause is considered an event.
Incidence of grade IV acute GVHD
-Graded according to the NIH consensus criteria.
Incidence of severe chronic GVHD
-Graded according to the NIH consensus criteria.
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