MAGIC Ruxolitinib for aGVHD (MAGIC V)

Phase 2 Study of Ruxolitinib-Based Primary Treatment for Acute GVHD

This clinical trial will study ruxolitinib-based treatment of acute graft-versus-host-disease (GVHD) that developed following allogeneic hematopoietic cell transplant. Acute GVHD occurs when donor cells attack the healthy tissue of the body. The most common symptoms are skin rash, jaundice, nausea, vomiting, and/or diarrhea. The standard treatment for GVHD is high dose steroids such as prednisone or methylprednisolone, which suppresses the donor cells, but sometimes there can be either no response or the response does not last. In these cases, the GVHD can become dangerous or even life threatening. High dose steroid treatment can also cause serious complications. Researchers have developed a system, called the Minnesota risk system, to help predict how well the GVHD will respond to steroids based on the symptoms present at the time of diagnosis. The Minnesota risk system classifies patients with newly diagnosed acute GVHD into two groups with highly different responses to standard steroid treatment and long-term outcomes. This protocol maximizes efficiency because all patients with grade II-IV GVHD are eligible for screening and treatment is assigned according to patient risk. Patients with lower risk GVHD, Minnesota standard risk, have high response rates to steroid treatment. In this trial the researchers will test whether ruxolitinib alone is as effective (non-inferior) as steroid-free therapy and safe. Patients will be randomized to two different doses of ruxolitinib to identify the dose which maximizes efficacy while minimizing toxicities such as hematologic and infectious toxicities. Patients with higher risk GVHD, Minnesota high risk, have unacceptable outcomes with systemic corticosteroid treatment alone and the researchers will test whether adding ruxolitinib, a proven effective second line GVHD treatment, can improve outcomes when added to systemic corticosteroids as first line treatment.

Study Overview

• Status: Recruiting
• Conditions: Adverse Effects; Acute Graft-versus-host Disease; Allogeneic Bone Marrow Transplantation
• Intervention / Treatment: Drug: Ruxolitinib; Drug: Methylprednisolone

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rachel Young, BA; Phone Number: 646-937-1246; Email: rachel.young@mssm.edu
• Study Contact Backup: Name: Janna Baez, MA; Phone Number: 646-937-1552; Email: janna.baez@mssm.edu

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Comprehensive Cancer Center
      • Principal Investigator: Monzr Al Malki
      • Contact: Monzr Al Malki, MD; Phone Number: 626-256-4673; Email: malmalki@coh.org
  • Florida
    • Tampa, Florida, United States, 33612
      • Not yet recruiting
      • Moffitt Cancer Center
      • Principal Investigator: Joseph Pidala
      • Contact: Joseph Pidala, MD, PhD; Phone Number: 813-745-2556; Email: joseph.pidala@moffitt.org
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute, Emory University
      • Principal Investigator: Amelia Langston
      • Contact: Amelia Langston, MD; Phone Number: 404-441-7572; Email: alangst@emory.edu
  • Kansas
    • Fairway, Kansas, United States, 66205
      • Recruiting
      • Kansas University Medical Center
      • Contact: Umair Mushtaq, MD; Phone Number: 913-945-5793; Email: mmushtaq@kumc.edu
      • Principal Investigator: Umair Mushtaq, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Zachariah DeFilipp, MD; Phone Number: 617-726-5743; Email: zdefilipp@mgh.harvard.edu
      • Principal Investigator: Zachariah DeFilipp
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Dana Farber Cancer Institute
      • Contact: Corey Cutler, MD, MPH; Phone Number: 617-632-5946; Email: corey_cutler@dfci.harvard.edu
      • Principal Investigator: Corey Cutler
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: William Hogan, MB, ChB; Phone Number: 507-284-2176; Email: hogan.william@mayo.edu
      • Principal Investigator: William Hogan
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Not yet recruiting
      • Washington University
      • Principal Investigator: Iskra Pusic
      • Contact: Iskra Pusic, MD, MSCI; Phone Number: 314-747-8465; Email: iskrapusic@wustl.edu
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Contact: John Levine, MD, MS; Phone Number: 212-241-1469; Email: john.levine@mssm.edu
      • Principal Investigator: John Levine
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Not yet recruiting
      • Ohio State University
      • Contact: Hannah Choe, MD; Phone Number: 614-293-1396; Email: Hannah.Choe@osumc.edu
      • Principal Investigator: Hannah Choe
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Not yet recruiting
      • University of Pennsylvania
      • Principal Investigator: Elizabeth Hexner, MD
      • Contact: Elizabeth Hexner, MD; Phone Number: 215-614-1847
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Recruiting
      • Vanderbilt University
      • Principal Investigator: Carrie Kitko, MD
      • Contact: Carrie Kitko, DM; Phone Number: 615-936-2088; Email: carrie.l.kitko@vumc.org
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Amin Alousi, MD; Phone Number: 713-745-8613; Email: aalousi@mdanderson.org
      • Principal Investigator: Amin Alousi
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Research Center
      • Contact: Marco Mielcarek, MD; Phone Number: 206-667-2827; Email: mmielcar@fredhutch.org
      • Principal Investigator: Marco Mielcarek

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Standard risk cohort: Minnesota standard risk GVHD (except patients with grade I [<50% BSA rash])
• High risk cohort: Minnesota high risk GVHD 3 GVHD that developed after DLI for mixed chimerism or poor graft function is allowed
• No prior systemic acute GVHD treatment. Topical or non-absorbed steroids are permitted.
• All donor types, HLA-matches, conditioning regimens, or GVHD prophylaxis strategies are acceptable
• ≥18 years of age
• Standard risk cohort: Hematopoietic engraftment with absolute neutrophil count (ANC) ≥ 1000/μL and platelet count ≥20,000. Use of growth factor supplementation and transfusions to maintain adequate hematologic parameters are allowed.
• High risk cohort: Hematopoietic engraftment with ANC ≥ 500/uL and platelet count ≥20,000. Use of growth factor supplementation and transfusions to maintain adequate hematologic parameters are allowed.

Exclusion Criteria:

• Systemic treatment with ruxolitinib or any other JAK inhibitor within 7 days of study entry
• Prior use of ruxolitinib to treat GVHD at any time
• Relapsed, progressing or persistent malignancy requiring withdrawal of systemic immunosuppression
• Relapse prior to development of GVHD unless subsequently in remission for at least 3 months
• GVHD that developed after DLI for relapse is not allowed without study PI or medical monitor approval
• Uncontrolled infection (i.e., progressive symptoms related to infection despite treatment or persistently positive microbiological cultures despite treatment or any other evidence of severe sepsis)
• Severe organ dysfunction within 3 days of enrollment including requirement for dialysis, mechanical ventilation, continuous BiPAP, or continuous high flow oxygen by nasal cannula, or total bilirubin ≥ 3x upper limit of normal not due to GVHD.
• A clinical presentation resembling de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment (except for mild oral or ocular GVHD)
• Corticosteroids >10 mg/day methylprednisolone (or other methylprednisolone equivalent, MPE) for any indication within 5 days before the onset of acute GVHD except for adrenal insufficiency or premedication for transfusions/IV meds
• Participation in clinical trials using experimental agents not approved by the FDA for any indication within 14 days of enrollment or five half-lives, whichever is longer provided any prior adverse events have improved to ≤grade 1
• Patients who are pregnant or nursing
• History of allergic reaction to ruxolitinib or any JAK inhibitor

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Minnesota Standard Risk lower dose; Patients receive lower dose ruxolitinib orally (PO) twice daily (BID) for 56 days then begin taper PO once daily (QD) for 1 week in the absence of disease progression or unacceptable toxicity	Drug: Ruxolitinib; Ruxolitinib twice daily for 56 days followed by a short taper Given orally; Other Names: Jakafi
Experimental: Minnesota Standard Risk higher dose; Patients receive higher dose ruxolitinib PO BID for 56 days then begin taper PO BID for 1 week, followed by PO QD for 1 week in the absence of disease progression or unacceptable toxicity.	Drug: Ruxolitinib; Ruxolitinib twice daily for 56 days followed by a short taper Given orally; Other Names: Jakafi
Experimental: Minnesota High Risk; Patients receive higher dose ruxolitinib PO BID for 56 days then begin taper PO BID for 1 week, followed by PO QD for 1 week in the absence of disease progression or unacceptable toxicity. Patients also receive systemic corticosteroid (methylprednisolone or similar) for a minimum of 3 days, then taper dose every 3-5 days in the absence of disease progression or unacceptable toxicity.	Drug: Ruxolitinib; Ruxolitinib twice daily for 56 days followed by a short taper Given orally; Other Names: Jakafi; Drug: Methylprednisolone; Starting dose 2 mg/kg/d for at least three days, then taper Given IV or orally; Other Names: Depo-Medrol; Medrol; Solu-Medrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Day 28 Treatment Response	Day 28 response to treatment defined as complete (CR), very good partial (VGPR), or partial (PR) response without intervening therapy or death to ruxolitinib monotherapy. CR - All evaluable organs (skin, liver, GI tract) stage 0. For a response to be scored as CR, the patient must be in CR on the date of assessment and have had no intervening additional GVHD therapy. VGPR - Stage 0 liver and GI and residual stage 1 skin GVHD. For a response to be scored as VGPR, the patient must be in VGPR on the date of assessment and have had no intervening additional GVHD therapy. PR - An improvement by one or more stages in one or more organ involved with GVHD symptoms without worsening in others. For a response to be scored as PR, the patient must be in PR on the date of assessment and have had no intervening additional GVHD therapy.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steroid-refractory GVHD	Steroid Refractory (SR) GVHD is defined as GVHD that either does not achieve a clinical response or an additional line of therapy is initiated by day 28 from the initiation of systemic steroid therapy for non-responsive GVHD.	28 days
Durable response at day 56	Durable response at day 56 is defined as CR, VGPR, or PR by day 28 and no GVHD flare, intervening treatment or death by day 56	56 days
GVHD flares	Flare is defined as an increase in acute GVHD severity in at least one target organ by at least one stage that is treated with an additional line of treatment or an increase in steroid dose in methylprednisolone equivalents (MPE) by at least 25%	90 days
Cumulative systemic corticosteroid dose		90 days
Chronic GVHD requiring systemic steroid treatment		1 year
Overall survival	OS (overall survival) - defined as the time from the enrollment to death	1 year
Non-relapse mortality	Non-relapse mortality (NRM) - defined as any death that occurs after HCT not attributable to relapse of the underlying disease for transplant	1 year
Relapse	Relapse - defined as reoccurrence of the underlying disease for transplant	1 year

Collaborators and Investigators

• Sponsor: John Levine
• Collaborators: National Cancer Institute (NCI); Incyte Corporation
• Investigators: Principal Investigator: John Levine, MD, MS, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): April 14, 2028

Study Registration Dates

• First Submitted: April 12, 2025
• First Submitted That Met QC Criteria: April 12, 2025
• First Posted (Actual): April 20, 2025

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; ruxolitinib
• Other Study ID Numbers: STUDY-24-01656; P01CA039542 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Patient did not consent to this

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No