Recruiting
Phase 2

Ruxolitinib

Sponsor:

John Levine

Code:

NCT06936566

Conditions

Acute Graft-versus-host Disease

Allogeneic Bone Marrow Transplantation

Adverse Effects

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Ruxolitinib

Methylprednisolone

Study Details

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

Allogeneic Bone Marrow Transplantation

Adverse Effects

Study ID

NCT06936566

Start date

May 14, 2025

Status verified date

Mar, 2026

Completion date

Apr 14, 2028

Anticipated

Primary completion date

Jun 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

98 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

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.

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.

Interventions

Ruxolitinib

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

Methylprednisolone

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

Primary outcome measure

  • Day 28 Treatment Response [ Time Frame: 28 days ]

Central Contacts and Locations

Central contacts

Rachel Young, BA

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

Janna Baez, MA

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

Locations

City of Hope Comprehensive Cancer Center

Recruiting

Duarte, California, United States, 91010

Contacts

Monzr Al Malki, MD

626-256-4673malmalki@coh.org

Principal Investigator:

Monzr Al Malki

Winship Cancer Institute, Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Amelia Langston, MD

404-441-7572alangst@emory.edu

Principal Investigator:

Amelia Langston

Kansas University Medical Center

Recruiting

Fairway, Kansas, United States, 66205

Contacts

Umair Mushtaq, MD

913-945-5793mmushtaq@kumc.edu

Principal Investigator:

Umair Mushtaq, MD

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Zachariah DeFilipp, MD

617-726-5743zdefilipp@mgh.harvard.edu

Principal Investigator:

Zachariah DeFilipp

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Corey Cutler, MD, MPH

617-632-5946corey_cutler@dfci.harvard.edu

Principal Investigator:

Corey Cutler

Mayo Clinic

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

William Hogan, MB, ChB

507-284-2176hogan.william@mayo.edu

Principal Investigator:

William Hogan

Icahn School of Medicine at Mount Sinai

Recruiting

New York, New York, United States, 10029

Contacts

John Levine, MD, MS

212-241-1469john.levine@mssm.edu

Principal Investigator:

John Levine

Vanderbilt University

Recruiting

Nashville, Tennessee, United States, 37235

Contacts

Carrie Kitko, DM

615-936-2088carrie.l.kitko@vumc.org

Principal Investigator:

Carrie Kitko, MD

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Amin Alousi, MD

713-745-8613aalousi@mdanderson.org

Principal Investigator:

Amin Alousi

Fred Hutchinson Cancer Research Center

Recruiting

Seattle, Washington, United States, 98109

Contacts

Marco Mielcarek, MD

206-667-2827mmielcar@fredhutch.org

Principal Investigator:

Marco Mielcarek

More Information

Sponsor

John Levine

Last update posted

Mar 23, 2026

Last verified

Mar, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by John Levine on 2026-03-23.