RGI-2001 for the Prevention of Acute Graft-vs-Host Disease in Subjects Following Allogeneic Hematopoietic Stem Cell Transplantation

An Open Label Phase 2, Study to Evaluate the Safety and Efficacy of RGI-2001 for the Prevention of Acute Graft-vs-Host Disease Compared to Contemporary Controls in Subjects Following Allogeneic Hematopoietic Stem Cell Transplantation

This Phase II open label study will evaluate the safety and efficacy of repeat doses of RGI-2001 in combination with standard of care treatment for the prevention of acute graft-vs-host-disease (aGvHD) in subjects following Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT). These subjects will be compared to contemporary controls.

Study Overview

• Status: Completed
• Conditions: Graft Vs Host Disease; Graft-versus-host-disease; Acute-graft-versus-host Disease; Prevention of aGVHD
• Intervention / Treatment: Drug: RGI-2001; Drug: Standard of Care

Detailed Description

This is an open-label, multi-center, single-arm study to evaluate six weekly doses of RGI-2001 in combination with standard of care treatment for the prevention of aGvHD in subjects following alloHSCT. The study will include a Safety Run-in Phase to assess the safety and tolerability of 6 weekly doses of RGI-2001 followed by an Expansion Phase in which the potential efficacy of 6 weekly doses of RGI-2001 in addition to standard of care for GvHD prophylaxis will be assessed. Comparison will be made to a contemporaneous control group.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami, Sylvester Comprehensive Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • New York
    • New York, New York, United States, 10087-6453
      • Columbia University Irving Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Wexner Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ages ≥ 18 and ≤ 65 years of age
2. Has a hematologic malignancy which includes Acute myelogenous leukemia (AML), T or B cell acute lymphoblastic leukemia (ALL) Myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), myeloproliferative disorder (MPD) including myeloid metaplasia and CML
3. Must have adequate organ function
4. Transplant Donor: Matched related donor or Unrelated donor
5. Is a candidate for anti-graft-vs-host-disease (GvHD) prophylaxis that includes a calcineurin inhibitor
6. Ability to understand and willingness to sign a written informed consent form
7. If female of childbearing potential, must have had a negative serum pregnancy test prior to enrollment and must have agreed to use a double barrier method of contraception for 30 days after RGI-2001 administration
8. If male, must be sterile or willing to use an approved method of contraception from the time of informed consent to 90 days after last dose of RGI-2001 administration

Exclusion Criteria:

1. Has had any other prior organ transplantation
2. Planned procedure to deplete regulatory T cells from donor transplant materials
3. Planned reduced intensity conditioning
4. Has had prior treatment with anti-CD3, other T cell depleting antibodies, or anti-thymocyte globulin within 12 months prior to alloHSCT procedure
5. Has progressive underlying malignant disease including post-transplant lymphoproliferative disease
6. Has evidence of active central nervous system (CNS) disease including known brain or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of CNS involvement)
7. Is female and pregnant or lactating
8. Has a documented history of uncontrolled autoimmune disease or on active treatment
9. History of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to receiving study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RGI-2001; Subjects will be administered RGI 2001 in combination with standard of care treatment	Drug: RGI-2001; Subjects will receive 6 weekly doses of RGI 2001, 100 μg/kg via IV administration after completion of alloHSCT; Other Names: KRN-7000; RGI-7000; Drug: Standard of Care; Standard of care prophylaxis regimen will be administered according to institutional guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grades II-IV aGVHD	Acute GVHD will be graded and assessed according to modified KEYSTONE criteria and the severity grade (Grade II through IV) were captured up through the first 100 days post-transplant	Day 100 post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grades II-IV aGVHD	Acute GVHD will be graded and assessed within 180 days post-transplant	Day 180 post-transplant
Non-relapse Mortality (NRM) Rates	The probability of mortality not preceded by relapse of the underlying malignancy will be estimated	1 year post-transplant
Disease-free Survival (DFS)	The probability of survival without relapse of the underlying malignancy will be estimated	1 year post-transplant
GvHD-free, Relapse Free Survival (GRFS)	The probability of survival without relapse of the underlying malignancy, without severe (grades 3-4) acute GVHD, and without chronic GVHD requiring systemic immunosuppression will be estimated	1 year post-transplant
Overall Survival (OS)	The probability of survival will be estimated	1 year post-transplant

Collaborators and Investigators

• Sponsor: Regimmune Corporation
• Investigators: Principal Investigator: Yi-Bin Chen, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2019
• Primary Completion (Actual): July 5, 2022
• Study Completion (Actual): April 3, 2023

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (Actual): July 10, 2019

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; KRN 7000
• Other Study ID Numbers: RGI-2001-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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