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)

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.

Study Overview

• Status: Recruiting
• Conditions: Immune System Diseases; Autoimmune Lymphoproliferative; Primary Immune Regulatory Disorder
• Intervention / Treatment: Drug: Emapalumab; Procedure: Stem Cell Transplant; Drug: Fludarabine and Dexamethasone

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Roni Tamari, MD; Phone Number: 646-608-3738
• Study Contact Backup: Name: Joseph Oved, MD; Phone Number: 646-888-3314; Email: ovedj@mskcc.org

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
      • Contact: Joseph Oved, MD; Phone Number: 646-888-3314
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
      • Contact: Joseph Oved, MD; Phone Number: 646-888-3314
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
      • Contact: Joseph Oved, MD; Phone Number: 646-888-3314
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
      • Contact: Joseph Oved, MD; Phone Number: 646-888-3314
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
      • Contact: Joseph Oved, MD; Phone Number: 646-888-3314
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Joseph Oved, MD; Phone Number: 646-888-3314
      • Contact: Jaap Jan Boelens, MD, PhD; Phone Number: 212-639-3643
    • Rockville Centre, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (Limited Protocol Activities)
      • Contact: Joseph Oved, MD; Phone Number: 646-888-3314

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 or 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 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 isolated IFNγ pathway
• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.	Procedure: Stem Cell Transplant; Participants in both groups will receive their standard-of-care stem cell transplant on Day 0.; Drug: Fludarabine and Dexamethasone; Fludarabine and dexamethasone for 5 days in a row on Days -22 through -18.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Engraftment	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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine Overall Survival (OS)	the duration of time between HCT and death due to any cause	5 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Sobi, Inc.
• Investigators: Principal Investigator: Joseph Oved, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: March 15, 2023
• First Submitted That Met QC Criteria: March 15, 2023
• First Posted (Actual): March 28, 2023

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Dexamethasone; Fludarabine; Stem Cell Transplant; Emapalumab; 23-040
• Additional Relevant MeSH Terms: Immune System Diseases; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Fludarabine
• Other Study ID Numbers: 23-040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. 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. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No