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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Once 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
Washington University School of Medicine
St Louis, Missouri, United States
RECRUITINGSafety 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
Time frame: Through 100 days post-transplant
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.
Time frame: From day of transplant (day 0) to 42 days (+/- 14 days) post transplant
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.
Time frame: From day of transplant (day 0) to 75 days (+/- 14 days) post transplant)
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.
Time frame: Through day +100
Event free survival (EFS)
-Death, disease recurrence or progression, and graft failure are considered events
Time frame: At 24 months post transplant
Overall survival (OS)
Death by any cause is considered an event.
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Time frame: At 24 months post transplant
Incidence of grade IV acute GVHD
-Graded according to the NIH consensus criteria.
Time frame: Weekly through day +100
Incidence of severe chronic GVHD
-Graded according to the NIH consensus criteria.
Time frame: Day 101 through 24 months
Change in Lansky/Karnofsky performance score
* Lansky is used for participants \<15.99 years of age * Karnofsky is used for participants \>16.00 years of age
Time frame: Day +100, Day +180, Day +365, and +24 months
Number of pulmonary toxicities
Time frame: Through 24 months
Number of neurologic/neurocognitive toxicities
Time frame: Through 24 months
Number of cardiac toxicities
Time frame: Through 24 months
Number of renal toxicities
Time frame: Through 24 months
Number of hepatic toxicities
Time frame: Through 24 months
Number of metabolic toxicities
Time frame: Through 24 months
Number of thyroid toxicities
Time frame: Through 24 months
Incidence and severity of acute GVHD
-Graded according to the NIH consensus criteria.
Time frame: From day +14 through Day +100
Incidence and severity of chronic GVHD
-Graded according to the NIH consensus criteria.
Time frame: From day +101 through 24 months
Number of participants with infections requiring hospitalizations
Time frame: Through 24 months
Immune reconstitution as measured by recovery of absolute neutrophil count
Time frame: Over 24 months
Immune reconstitution as measured by recovery of absolute monocyte count
Time frame: Over 24 months
Immune reconstitution as measured by regain of function of NK cell populations
* Immune reconstitution is defined as regain of function of donor-derived immunogenic cells. Immune reconstitution is to be measured by recovery of individual cellular compartments * Via flow cytometry
Time frame: Over 24 months
Immune reconstitution as measured by regain of function of T cell populations
* Immune reconstitution is defined as regain of function of donor-derived immunogenic cells. Immune reconstitution is to be measured by recovery of individual cellular compartments * Via flow cytometry
Time frame: Through 24 months
Immune reconstitution as measured by regain of function of B cell populations
* Immune reconstitution is defined as regain of function of donor-derived immunogenic cells. Immune reconstitution is to be measured by recovery of individual cellular compartments * Via flow cytometry
Time frame: Through 24 months
Immune reconstitution as measured by regain of function of immunoglobulin G (IgG)
* Immune reconstitution is defined as regain of function of donor-derived immunogenic cells. Immune reconstitution is to be measured by recovery of individual cellular compartments * Via serum analysis
Time frame: Over 24 months
Immune reconstitution as measured by regain of function of immunoglobulin A (IgA)
* Immune reconstitution is defined as regain of function of donor-derived immunogenic cells. Immune reconstitution is to be measured by recovery of individual cellular compartments * Via serum analysis
Time frame: Over 24 months
Immune reconstitution as measured by regain of function of immunoglobulin M (IgM)
* Immune reconstitution is defined as regain of function of donor-derived immunogenic cells. Immune reconstitution is to be measured by recovery of individual cellular compartments * Via serum analysis
Time frame: Over 24 months