A Study of Treatment of Inflammation Before Stem Cell Transplant in People With a Primary Immune Regulatory Disorder (PIRD) and/or an Autoinflammatory Condition

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05787574

Collaborator

Sobi, Inc. (Industry)

Enrollment

Locations

Arms

47.5

Anticipated Duration (Months)

5.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Immune Regulatory Disorder Autoimmune Lymphoproliferative Immune System Diseases	Drug: Emapalumab Drug: Fludarabine and Dexamethasone Procedure: Stem Cell Transplant	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

39 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a two-stage phase 2 study.This is a two-stage phase 2 study.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 2 Study BRIDGING PRE-TRANSPLANT INFLAMMATORY DAMPENING for PRIMARY IMMUNE REGULATORY DISORDERS (BRIDGE Trial)

Actual Study Start Date :

Mar 15, 2023

Anticipated Primary Completion Date :

Mar 1, 2027

Anticipated Study Completion Date :

Mar 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A: Emapalumab (for isolated Interferongamma mediated disease) Participants in this group will receive emapalumab on Days -22 (22 days before the day of the stem cell transplant), -15, -8, and -1.	Drug: Emapalumab Emapalumab on Days -22 (22 days before the day of the stem cell transplant), -15, -8, and -1. Procedure: Stem Cell Transplant Participants in both groups will receive their standard-of-care stem cell transplant on Day 0.
Experimental: Group B: Fludarabine and Dexamethasone (for generalized autoinflammation) Participants in this group will receive fludarabine and dexamethasone for 5 days in a row on Days -22 through -18.	Drug: Fludarabine and Dexamethasone Fludarabine and dexamethasone for 5 days in a row on Days -22 through -18. Procedure: Stem Cell Transplant Participants in both groups will receive their standard-of-care stem cell transplant on Day 0.

Arm

Intervention/Treatment

Experimental: Group A: Emapalumab (for isolated Interferongamma mediated disease)

Participants in this group will receive emapalumab on Days -22 (22 days before the day of the stem cell transplant), -15, -8, and -1.

Drug: Emapalumab

Emapalumab on Days -22 (22 days before the day of the stem cell transplant), -15, -8, and -1.

Procedure: Stem Cell Transplant

Participants in both groups will receive their standard-of-care stem cell transplant on Day 0.

Experimental: Group B: Fludarabine and Dexamethasone (for generalized autoinflammation)

Participants in this group will receive fludarabine and dexamethasone for 5 days in a row on Days -22 through -18.

Drug: Fludarabine and Dexamethasone

Fludarabine and dexamethasone for 5 days in a row on Days -22 through -18.

Procedure: Stem Cell Transplant

Participants in both groups will receive their standard-of-care stem cell transplant on Day 0.

Outcome Measures

Primary Outcome Measures

Engraftment [1 year]
is defined as the first of three days of absolute neutrophil count >500k/µL and the first of seven days of platelets >20,000/µL in the absence of transfusional support.

Secondary Outcome Measures

Determine Overall Survival (OS) [5 years]
the duration of time between HCT and death due to any cause

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients receiving first allo-HCT for the following immunologic conditions:
Primary Immune Regulatory Disorder with or without a genetic lesion as defined by the Primary Immune Deficiency Treatment Consortium (PIDTC)
Patients with autoinflammatory disorders evidenced by cytokine and inflammation assays with at least 1.5x ULN of measured cytokines and/or an elevated ferritin or ESR > 2 ULN
For inclusion on the emapalumab group, the lesion must be isolated to the IFNγ pathway (or mediators thereof) with an elevated CXCL9 >1.5 ULN (or already controlled on a JAK inhibitor, provided that CXCL9 levels were elevated prior to initiation of the JAK inhibitor). Inclusion on the Fludarabine/dexamethasone group requires inflammation (as defined above) other than an isolated IFNγ/CXCL9 defect
Able to tolerate cytoreduction (based on adequate organ function as described below)
Patients of any age can enroll so long as they meet other inclusion criteria:
Adequate organ function is required, defined as follows:
Hepatic: Serum bilirubin ≤ 2 mg/dL, unless benign congenital hyperbilirubinemia. Patients with hyperbilirubinemia related to paroxysmal nocturnal hemoglobinuria or other hemolytic disorders related to their PIRD diagnosis are eligible.
Hepatic: AST, ALT, and alkaline phosphatase < 2.5 times the upper limit of normal unless thought to be disease-related. Investigator will need to perform clinically indicated evaluations to assess if disease related or intrinsic liver disease. Additional testing may be done if clinically indicated, after the pre-transplant immune prophase and prior to start of conditioning as this will provide additional data to confirm disease related versus intrinsic liver dysfunction.
Renal: serum creatinine <1.5x normal for age. If serum creatinine is outside the normal range, then CrCl > 50 mL/min/1.73m2 (calculated or estimated) or GFR (mL/min/1.72m2) >30% of predicted normal for age.
Normal GFR by Age
Cardiac: LVEF ≥ 50% by MUGA or resting echocardiogram.
Pulmonary: Pulmonary function testing (FEV1 and corrected DLCO) ≥ 50% predicted (pediatric patients unable to complete PFTs will need oxygen saturation as recorded by pulse oximetry of ≥92% on room air).
Adequate performance status:
Age ≥ 16 years: ECOG ≤ 1 or Karnofsky 70%
Age < 16 years: Lansky 70%
Each patient must be willing to participate as a research subject and must sign an informed consent form or legal guardian with assent as appropriate.

Exclusion Criteria:

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.
Patients unwilling to use contraception during the study period.
Patient or parent or guardian unable to give informed consent or unable to comply with the treatment protocol including research tests.

Donor Inclusion Criteria:

Related Donors:
8/8 or 7/8 HLA matched at A, B, C, and DRB1 loci, as tested by DNA analysis.
Haploidentical donors at A, B, C and DRB1 loci, as tested by DNA analysis
Unrelated Donors:

o 8/8 or 7/8 matched at A, B, C, and DRB1 loci, as tested by DNA analysis.

Able to provide informed consent for the donation process per institutional standards.
Meet standard criteria for donor collection (e.g. National Marrow Donor Program Guidelines or collecting center guidelines as approved by treating physician).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)	Commack	New York	United States	11725
5	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Rockville Centre	New York	United States	11553