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

Official title

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

Overview

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.

Interventions

• Drug Ruxolitinib
  Ruxolitinib is a Janus kinase inhibitor.
• Drug Prednisone
  Prednisone is a glucocorticoid.

Primary outcome measures

• Treatment Success [Time frame: 6 months]

Secondary outcome measures (1)

• Treatment Success Rate [Time frame: 6 months]

Eligibility criteria

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:

• absolute neutrophil count ≥1,000/mcL
• platelets ≥30,000/mcL
• Hemoglobin ≥ 7 g/dL
• 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. Molecular relapse or Mixed chimerism or treated relapse in remission may be allowed on case by case basis but needs discussion with the study Chair/PI
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 6 centers

• Univ of Miami - Sylvester Comprehensive Cancer Center — Miami
• Moffitt Cancer Center — Tampa
• University of Kansas Cancer Center — Kansas City
• Fox Chase Cancer Center — Philadelphia
• University of Virginia Comprehensive Cancer Center — Charlottesville
• Virginia Commonwealth University — Richmond

Identifiers

NCT: NCT06660355 · MCC-23051

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗