MAGIC Ruxolitinib for aGVHD

NCT06936566 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY-24-01656P01CA039542
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 14

Brief Summary

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.

Conditions

Acute Graft-versus-host Disease; Adverse Effects; Allogeneic Bone Marrow Transplantation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Steroid-refractory GVHD

  28 days

• Durable response at day 56

  56 days

• GVHD flares

  90 days

• Cumulative systemic corticosteroid dose

  90 days

• Chronic GVHD requiring systemic steroid treatment

  1 year

Study Arms (3)

Minnesota Standard Risk lower dose

EXPERIMENTAL

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

Minnesota Standard Risk higher dose

EXPERIMENTAL

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

Minnesota High Risk

EXPERIMENTAL

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; Drug: Methylprednisolone

Interventions

Ruxolitinib DRUG

Ruxolitinib twice daily for 56 days followed by a short taper Given orally

Also known as: Jakafi

Minnesota High Risk; Minnesota Standard Risk higher dose; Minnesota Standard Risk lower dose

Methylprednisolone DRUG

Starting dose 2 mg/kg/d for at least three days, then taper Given IV or orally

Also known as: Depo-Medrol, Medrol, Solu-Medrol

Minnesota High Risk

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• John Levine: lead
• Incyte Corporation: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (14)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

NOT YET RECRUITING

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Kansas University Medical Center

Fairway, Kansas, 66205, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

NOT YET RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

NOT YET RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

NOT YET RECRUITING

Vanderbilt University

Nashville, Tennessee, 37235, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Interventions

ruxolitinib; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• John Levine, MD, MS

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel Young, BA

CONTACT

646-937-1246; rachel.young@mssm.edu

Janna Baez, MA

CONTACT

646-937-1552; janna.baez@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Internal Medicine and Pediatrics

Study Record Dates

• First Submitted: April 12, 2025
• First Posted: April 20, 2025
• Study Start: May 14, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): April 14, 2028
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)