The researchers are doing this study to find out whether emapalumab or a combination of fludarabine and dexamethasone are effective in preparing people with a primary immune regulatory disorder (PIRD) and/or an autoinflammatory condition to receive a stem cell transplant. The researchers will look at how well the study treatments reduce inflammation and aid in the engraftment process (the process of donated stem cells traveling to the bone marrow, where they begin to make new immune cells.
"Funding Source - FDA OOPD"
Primary Immune Regulatory Disorder with or without a genetic lesion as defined by the Primary Immune Deficiency Treatment Consortium (PIDTC)12 - Patients with autoinflammatory disorders evidenced by cytokine or inflammation assays with at least 1.5x ULN of measured cytokines (defined in section 4) and/or an elevated ferritin or ESR > 2 ULN
For inclusion on the emapalumab group, the lesion must be related to the IFNγ pathway (or mediators thereof) with an elevated CXCL9 >1.5 ULN OR sIL2R >1.5 ULN (or already controlled on immune modulation, provided that CXCL9 or sIL2R levels were elevated prior to initiation of immune modulation).
Inclusion on the Fludarabine/dexamethasone group requires inflammation (as defined above) other than an IFNy pathway defect
Able to tolerate cytoreduction (based on adequate organ function as described below)
Uncontrolled infection at the time of enrollment.
Patients who have undergone previous allo-HCT.
Patient seropositivity for HIV I/II and/or HTLV I/II.
Females who are pregnant or breastfeeding.
Parallel
Emapalumab
DrugEmapalumab on Days -22 (22 days before the day of the stem cell transplant), -15, -8, and -1.
Fludarabine and Dexamethasone
DrugFludarabine and dexamethasone for 5 days in a row on Days -22 through -18.
Allogeneic hematopoietic stem cell transplant (allo-HCT)
Procedure/SurgeryParticipants in both groups will receive their standard-of-care stem cell transplant on Day 0.
Engraftment
Engraftment is defined as the first of three days of absolute neutrophil count \>500,000/µL and the first of seven days of platelets \>20,000/µL in the absence of transfusional support.
Overall Survival (OS)
Overall Survival (OS) is defined as the duration of time between allo-HCT and death due to any cause.
Event Free Survival (EFS)
Event-Free Survival (EFS) is the length of time from the start of a treatment or study until a patient experiences a defined negative "event" (such as disease recurrence, progression, or death).
Non-Relapse Mortality (TRM)
Participants who die for any reason after disease recurrence are considered to have experienced disease related mortality, and will be counted as competing events. Patients alive will be censored at the day of last follow up.
GVHD free/relapse free survival (GRFS)
Duration of time between transplantation and development of grade III-IV GVHD, chronic GVHD requiring systemic therapy, disease relapse, or death, whichever occurs first.
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