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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Graft Vs Host Disease, Graft-versus-host-disease, Acute-graft-versus-host Disease, Prevention of aGVHD

Intervention / Treatment
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* Drug: RGI-2001
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages ≥ 18 and ≤ 65 years of age 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 Must have adequate organ function Transplant Donor: Matched related donor or Unrelated donor Is a candidate for anti-graft-vs-host-disease (GvHD) prophylaxis that includes a calcineurin inhibitor Ability to understand and willingness to sign a written informed consent form 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 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: Has had any other prior organ transplantation Planned procedure to deplete regulatory T cells from donor transplant materials Planned reduced intensity conditioning Has had prior treatment with anti-CD3, other T cell depleting antibodies, or anti-thymocyte globulin within 12 months prior to alloHSCT procedure Has progressive underlying malignant disease including post-transplant lymphoproliferative disease 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) Is female and pregnant or lactating Has a documented history of uncontrolled autoimmune disease or on active treatment History of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to receiving study drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grades II-IV aGVHD | Acute GVHD will be graded and assessed within 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 | Day 100, 6 months and 1 year post-transplant | 
| Disease-free survival (DFS) | The probability of survival without relapse of the underlying malignancy will be estimated | 6 months and 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 | 6 months and 1 year post-transplant | 
| Overall survival (OS) | The probability of survival will be estimated | 6 months and 1 year post-transplant |