Ruxolitinib vs Prednisone as First-line Therapy for cGVHD Needing Systemic Therapy

Phase II Randomized Study of Ruxolitinib vs Prednisone as First-Line Therapy for Chronic Graft vs Host Disease Needing Systemic Therapy

Allogeneic transplant is potentially curative for hematological malignancies but its use is limited by the development of GVHD. Ruxolitinib now has FDA approval for treatment of chronic GVHD that has failed 1-2 prior lines of therapy based on a prior large, randomized phase III study. Given this evidence of safety and efficacy in the early refractory setting (after prednisone failure), Ruxolitinib represents an ideal agent to test in the primary therapy setting. Here investigators propose a phase 2 randomized study to compare Ruxolitinib to prednisone as a first-line therapy in the treatment of chronic GVHD.

Study Overview

• Status: Recruiting
• Conditions: Chronic Graft-versus-host Disease (cGVHD)
• Intervention / Treatment: Drug: Ruxolitinib; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sarah Starr; Phone Number: 813-745-2690; Email: Sarah.Starr@moffitt.org

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • Univ of Miami - Sylvester Comprehensive Cancer Center
      • Principal Investigator: Noa Holtzman, MD
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Principal Investigator: Farhad Khimani, MD
      • Sub-Investigator: Melissa Alsina, MD
      • Sub-Investigator: Jose Ochoa-Bayona, MD
      • Sub-Investigator: Lia Perez, MD
      • Sub-Investigator: Joseph Pidala, MD, PhD
      • Sub-Investigator: Doris Hansen, MD
      • Sub-Investigator: Rawan Faramand, MD
      • Sub-Investigator: Hien Liu, MD
      • Sub-Investigator: Omar Castaneda Puglianini, MD
      • Sub-Investigator: Frederick Locke, MD
      • Sub-Investigator: Asmita Mishra, MD
      • Sub-Investigator: Taiga Nishihori, MD
      • Sub-Investigator: Michael Jain, MD, PhD
      • Sub-Investigator: Nelli Bejanyan, MD
      • Sub-Investigator: Aleksandr Lazaryan, MD, PhD
      • Sub-Investigator: Sayeef Mirza, MD
      • Sub-Investigator: Hany Elmariah, MD
      • Sub-Investigator: Ciara Freeman, MD, PhD
      • Sub-Investigator: Fabiana Perna, MD, PhD
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Cancer Center
      • Principal Investigator: Muhammad Umair Mushtaq, MD
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia Comprehensive Cancer Center
      • Principal Investigator: Indumathy Varadarajan, MD
    • Richmond, Virginia, United States, 23219
      • Recruiting
      • Virginia Commonwealth University
      • Principal Investigator: William Clark, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Karnofsky performance status ≥60%.
• Patients with a diagnosis of chronic GVHD per NIH diagnostic criteria5 who are in need for first systemic therapy as per treating physician's discretion, Overlap chronic GVHD will be allowed.
• No new immune suppressive therapy added within preceding 2 weeks prior to study enrolment.
• Able to take oral medications.

• Participants must have adequate organ and marrow function as defined below:

  1. absolute neutrophil count ≥1,000/mcL
  2. platelets ≥30,000/mcL
  3. Hemoglobin ≥ 7 g/dL
  4. Bilirubin ≤ 3 times institutional upper limit of normal (ULN) unless attributable to GVH

  d. AST(SGOT)/ALT(SGPT) ≤5 × institutional ULN unless attributable to GVH e. creatinine clearance ≥30 ml/min

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study drug administration.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Previously treated with systemic immune suppressive therapy for chronic GVHD (where the indication for start of that systemic immune suppressive therapy was chronic GVHD).
• Patients with clinically significant or uncontrolled cardiovascular disease, including unstable angina, acute myocardial infarction, or stroke within 6 months, New York Heart Association class III or IV heart failure will be excluded.
• Relapse malignancy post- transplant.
• Active hepatitis B, hepatitis C and HIV will be excluded.
• Any uncontrolled infection at the time if enrollment will be excluded.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ruxolitinib.
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women and lactating women are excluded from this study because of the potential for teratogenic or abortifacient effects and an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Ruxolitinib, breastfeeding should be discontinued if the mother is treated with Ruxolitinib.
• Current or history of active Tuberculosis.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ruxolitinib Treatment Arm; Ruxolitinib is administered as 10 mg orally twice daily in 28-day cycles.	Drug: Ruxolitinib; Ruxolitinib is a Janus kinase inhibitor.
Active Comparator: Prednisone Treatment Arm; Prednisone will be started at 1mg/kg/day based on patient current body weight in kilograms.	Drug: Prednisone; Prednisone is a glucocorticoid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Success	Treatment Success is defined as C7D1 NIH CR/PR without death or new line of immune suppressive therapy and will be estimated for both arms.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Success Rate	The proportion of subjects who are alive with NIH CR/PR, no new systemic therapy for cGVHD, and < 0.25 mg/kg/day prednisone at C7D1 with 95% CI for each arm will be estimated.	6 months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: Incyte Corporation
• Investigators: Principal Investigator: Farhad Khimani, MD, Moffitt Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: October 24, 2024
• First Submitted That Met QC Criteria: October 24, 2024
• First Posted (Actual): October 28, 2024

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organizing Pneumonia; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Prednisone; ruxolitinib
• Other Study ID Numbers: MCC-23051

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