Trial Outcomes & Findings for Allogeneic Hematopoietic Stem Cell Transplantation With Briquilimab-Based Conditioning in Participants With GATA2 Deficiency (NCT NCT05907746)

Allogeneic Hematopoietic Stem Cell Transplantation With Briquilimab-Based Conditioning in Participants With GATA2 Deficiency

To determine whether allogeneic hematopoietic cell transplantation with Briquilimab-based conditioning results in sustained donor engraftment by 100 days post-transplant, the percentage of evaluable participants with GATA2 deficiency will be reported along with a two-sided 90% confidence interval. Sustained donor engraftment is defined as neutrophil recovery with ANC ≥ 500/mm\^3 for 3 consecutive days associated with \>90% myeloid and \>10% cluster of differentiation 3 (CD3+) T cell donor chimerism by 100 days post-transplant.

To determine whether allogeneic hematopoietic cell transplantation with Briquilimab-based conditioning results in sustained donor engraftment by 100 days post-transplant, the percentage of evaluable participants with GATA2 deficiency will be reported along with a two-sided 95% confidence interval. Sustained donor engraftment is defined as neutrophil recovery with ANC ≥ 500/mm\^3 for 3 consecutive days associated with \>90% myeloid and \>10% cluster of differentiation 3 (CD3+) T cell donor chimerism by 100 days post-transplant and restoration of normal hematopoiesis by one-year post-transplant.

To determine whether allogeneic hematopoietic cell transplantation with Briquilimab-based conditioning results in restoration of normal hematopoiesis by one-year post-transplant in participants with GATA2 deficiency the percentage of evaluated participants will be reported along with a 95% two-sided confidence interval. Restoration of normal hematopoiesis is defined as normalization of peripheral blood counts hemoglobin (Hb) \>8 g/dL, platelet count \> 100,000/µ/L and absolute neutrophil count (ANC)\>1,500/µ/L).

By Arm, the participants with transplant-related toxicity will be reported by type and grade of event. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild. Grade 2 is moderate. Grade 3 is serious. Grade 4 is life-threatening. Grade 5 is death related to adverse event.

OS is defined as time from treatment start date until death from any cause, last follow up or date last known alive. OS was determined by using the Kaplan-Meier method and is reported along with the median value and the 95% confidence interval.

EFS is defined as death, receipt of a second transplant, or graft failure. EFS was determined using the Kaplan-Meier method and is reported along with the median value and the 95% confidence interval. Primary graft failure is defined as the lack of donor-derived neutrophil engraftment by day +60 after transplant. Secondary graft failure is defined as initial donor-derived neutrophil engraftment followed by the subsequent loss of donor chimerism to \< 10% donor whole blood or myeloid peripheral blood chimerism.

Percentage of participants with secondary graft failure at 3 years is reported separately by cohort along with 95% two-sided confidence interval. Secondary graft failure is defined as initial donor-derived neutrophil engraftment followed by the subsequent loss of donor chimerism to \< 10% donor whole blood or myeloid peripheral blood chimerism within 3 years after transplant.

Incidence of grades III-IV acute and moderate to severe chronic graft versus host disease within 3 years after transplant will be reported separately by cohort using simple estimates along with 95% two-sided confidence intervals. In addition, cumulative incidence curves along with 95% two-sided confidence interval. Acute GVHD staging and grading will be assessed according to the 1994 Consensus Conference on Acute GVHD Grading criteria. Grade III liver (bilirubin) stage 2-3 or stage 2.4 gut (stool output per day). Grade IV is stage 4 (skin) or stage 4 liver (bilirubin). Chronic GVHD diagnosis and staging will be assessed according to the 2014 Chronic GVHD Consensus Project. Diagnostic signs and symptoms of chronic GVHD are those that establish the diagnosis of chronic GVHD without need for further testing or evidence of other organ involvement.

Cumulative incidence curves accounting for the competing risk of transplant-related mortality will be constructed by cohort, with the values reported at day 100, one, and two years, along with a 95% two-sided confidence interval.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.