Clinical trial NCT06936566: MAGIC Ruxolitinib for aGVHD
Official title: Phase 2 Study of Ruxolitinib-Based Primary Treatment for Acute GVHD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Graft-versus-host Disease
Allogeneic Bone Marrow Transplantation
Adverse Effects
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Incyte Corporation
name: National Cancer Institute (NCI)
First posted: 2025-04-20
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Day 28 Treatment Response
timeFrame: 28 days
Secondary outcomes:
measure: Steroid-refractory GVHD
timeFrame: 28 days
measure: Durable response at day 56
timeFrame: 56 days
measure: GVHD flares
timeFrame: 90 days
measure: Cumulative systemic corticosteroid dose
timeFrame: 90 days
measure: Chronic GVHD requiring systemic steroid treatment
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
measure: Non-relapse mortality
timeFrame: 1 year
measure: Relapse
timeFrame: 1 year
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: John Levine, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: