A Study of Treatment of Inflammation Before Stem Cell Transplant in People With a Primary Immune Regulatory Disorder (PIRD) and/or an Autoinflammatory Condition
Phase 2 Study Bridging Pre-Transplant Inflammatory Dampening for Primary Immune Regulatory Disorders (BRIDGE Trial)
2 other identifiers
interventional
39
1 country
13
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. "Funding Source - FDA OOPD"
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Mar 2023
Typical duration for phase_2
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 15, 2023
CompletedStudy Start
First participant enrolled
March 15, 2023
CompletedFirst Posted
Study publicly available on registry
March 28, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2027
June 2, 2026
May 1, 2026
4 years
March 15, 2023
May 29, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
Day 100 post-alloHCT
Secondary Outcomes (18)
Overall Survival (OS)
1 year
Event Free Survival (EFS)
Up to 2 years post-alloHCT
Non-Relapse Mortality (TRM)
1 year
GVHD free/relapse free survival (GRFS)
1 year
Chronic graft vs host disease/relapse free survival (CRFS)
1 year
- +13 more secondary outcomes
Study Arms (2)
Group A: Emapalumab (for isolated Interferongamma mediated disease)
EXPERIMENTALParticipants in this group will receive emapalumab on Days -22 (22 days before the day of the stem cell transplant), -15, -8, and -1.
Group B: Fludarabine and Dexamethasone (for generalized autoinflammation)
EXPERIMENTALParticipants in this group will receive fludarabine and dexamethasone for 5 days in a row on Days -22 through -18.
Interventions
Emapalumab on Days -22 (22 days before the day of the stem cell transplant), -15, -8, and -1.
Fludarabine and dexamethasone for 5 days in a row on Days -22 through -18.
Participants in both groups will receive their standard-of-care stem cell transplant on Day 0.
Eligibility Criteria
You may qualify if:
- 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)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
- Able to tolerate cytoreduction (based on adequate organ function as described below)
- Patients of any age can enroll so long as they meet all other eligibility 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/1.73m\^2 (calculated or estimated) or GFR (mL/min/1.72m\^2) \>30% of predicted normal for 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.
- Related Donors:
- +6 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Joseph Ovedlead
- Sobi, Inc.collaborator
Study Sites (13)
University of California, San Francisco
San Francisco, California, 94143, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Suffolk - Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
Columbia University Irving Medical Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau
Rockville Centre, New York, 11553, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
MeSH Terms
Conditions
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Joseph Oved, MD
Columbia University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Associate Professor of Pediatrics (in Medicine)
Study Record Dates
First Submitted
March 15, 2023
First Posted
March 28, 2023
Study Start
March 15, 2023
Primary Completion (Estimated)
March 1, 2027
Study Completion (Estimated)
March 1, 2027
Last Updated
June 2, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals.