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

Phase 2

Completed

• Conditions: Graft Vs Host Disease; Prevention of aGVHD; Acute-graft-versus-host Disease; Graft-versus-host-disease
• Interventions: Drug: RGI-2001; Drug: Standard of Care

• Registration Number: NCT04014790
• Lead Sponsor: Regimmune Corporation

Brief Summary

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.

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 Timeline

• Study First Submitted: 2019-07-08
• Study First Submitted QC: 2019-07-08
• Study First Posted: 2019-07-10
• Study Start: 2019-11-25
• Primary Completion: 2022-07-05
• Study Completion: 2023-04-03
• Results First Submitted: 2024-01-17
• Status Verified: 2024-04
• Results First Submitted QC: 2024-04-08
• Results First Posted: 2024-04-17
• Last Update Submitted: 2024-04-29
• Last Update Posted: 2024-05-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RGI-2001	Standard of Care	Subjects will be administered RGI 2001 in combination with standard of care treatment
RGI-2001	RGI-2001	Subjects will be administered RGI 2001 in combination with standard of care treatment

Primary Outcome Measures

Name	Time	Method
Grades II-IV aGVHD	Day 100 post-transplant	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

Secondary Outcome Measures

Name	Time	Method
Disease-free Survival (DFS)	1 year post-transplant	The probability of survival without relapse of the underlying malignancy will be estimated
Non-relapse Mortality (NRM) Rates	1 year post-transplant	The probability of mortality not preceded by relapse of the underlying malignancy will be estimated
Overall Survival (OS)	1 year post-transplant	The probability of survival will be estimated
Grades II-IV aGVHD	Day 180 post-transplant	Acute GVHD will be graded and assessed within 180 days post-transplant
GvHD-free, Relapse Free Survival (GRFS)	1 year post-transplant	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

Trial Locations

Locations (7)

UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

University of Maryland Greenebaum Comprehensive Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Miami, Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

Ohio State University Wexner Medical Center; 🇺🇸 Columbus, Ohio, United States

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States