Topical Ruxolitinib for Cutaneous Chronic Graft Versus Host Disease (cGVHD)

Graft Versus Host Disease Clinical Trial

Official title: Phase II Study of Topical Ruxolitinib for Cutaneous Chronic Graft Versus Host Disease (cGVHD)

Status Terminated

Clinical Trial Summary

Background:

About half the people who have a hematopoietic stem cell transplant using donor cells get Chronic Graft Versus Host Disease (cGVHD). This is chronic graft versus host disease. Immune cells from the donor may see the body tissues in the person as foreign and attack, causing damage. The skin is the most commonly affected organ. Most cGVHD therapies have serious side effects. The cream ruxolitinib inhibits proteins that may play a role in cGVHD.

Objective:

To test the safety and effectiveness of topical ruxolitinib 1.5 percent cream in people with cGVHD of the skin.

Eligibility:

People ages 12 and older with epidermal skin cGVHD

Design:

Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Skin sample taken (biopsy) to confirm the diagnosis.

At the baseline visit, participants will have:

Skin disease measured with rulers, photographs, and tracing the outline of skin lesions

To complete questionnaires about their symptoms

Blood and urine tests

Some participants will also have a skin biopsy, or total body photographs while they wear only underwear.

Participants will get the ruxolitinib cream and a placebo cream to apply to 2 separate areas of disease. They will do this twice a day for 6 weeks, if they do not have serious side effects. Neither the study team nor the participant will know which area will get ruxolitinib cream and the placebo cream.

Participants will write down:

• When they apply the creams

• Any side effects

• Any medications they take

Most participants will have 4 visits during the 6 weeks they use the creams. Some will have 3 visits and a phone call to see how they are doing. All participants will get a call 4-6 weeks after they stop. Visits include physical exams, blood tests, skin disease measurements, questionnaires, and photos.

Clinical Trial Description

Background:

• Chronic graft-versus-host disease (cGVHD) develops in approximately half of individuals who undergo allogeneic hematopoietic cell transplant (HCT) and is the leading cause of non-relapse mortality.

• There are no skin-targeted therapies for cutaneous cGVHD that are directed to the pathogenesis of cGVHD.

• Many inflammatory cytokines involved in the pathogenesis of cGVHD signal through the Janus kinase (JAK)-Signal Transducer and Activator of Transcription (STAT) pathway.

• Systemic JAK inhibitors have been studied in GVHD murine models and in humans with improvement at the cellular and clinical level.

• Topical JAK inhibitors have not been studied in cutaneous cGVHD but have demonstrated the ability to decrease inflammatory markers as well as improve clinical findings of psoriasis.

Objectives:

• To determine the safety and tolerability of topical ruxolitinib 1.5% cream in patients with cutaneous cGVHD with epidermal involvement (non-sclerotic form)

• To determine the efficacy of topical ruxolitinib 1.5% cream in patients with cutaneous cGVHD with epidermal involvement (non-sclerotic form)

Eligibility:

Inclusion:

• Age greater than or equal to 12 years old

• Histologically confirmed epidermal cGVHD (including lichen planus-like, papulosquamous, erythematous) involving at least 2 separate, non-ulcerated sites that can be delineated by body region (e.g., right forearm and left forearm)

• Stable systemic cGVHD treatment including immunosuppressant therapy for 4 weeks prior to enrollment

• Karnofsky or Lansky score greater than or equal to 60%

Exclusion:

• Concurrent use of JAK inhibitors (topical or systemic), fluconazole, or strong Cytochrome P450 3A4 (CYP3A4) inhibitors

• Known hypersensitivity to JAK inhibitors or their components

• Active infection including cytomegalovirus (CMV), Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV)

• Recurrent or progressive malignancy requiring anticancer treatment

• Patients receiving other investigational agents

• Pregnancy

Design:

• This is a Phase II, placebo-controlled, double-blinded study to determine the safety, tolerability and efficacy of topical ruxolitinib in patients with epidermal cGVHD.

• Participants with at least 2 non-ulcerated sites of epidermal cGVHD will apply topical ruxolitinib 1.5% cream to 1 prespecified site and vehicle cream to the second prespecified site twice a day for 6 weeks.

• Safety will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. Assessments will occur during visits and/or phone follow-up every 2 weeks during treatment.

• Efficacy will be assessed at 6 weeks. The initial surface areas of the 2 target lesions will be measured at baseline, week 2, and week 6 on evaluable patients, with the option for an in-person assessment at week 4. The percent decline in the surface area of the 2 lesions will be determined, and the difference in decline between the 2 lesions will be calculated, expressed consistently as ruxolitinib decline minus placebo decline.

• A skin biopsy and peripheral blood samples will be collected prior to treatment and at week 6 to evaluate the cutaneous immune compartment cellular infiltrate, cytokine profiling, signal transducer and activator of transcription (STAT) phosphorylation, and in situ cGVHD biomarkers.

• Pharmacokinetic studies will be performed at week 2.

• Up to 15 patients will be enrolled to achieve 10 evaluable patients, defined as participants who remain active at the time of the primary endpoint. 10 evaluable patients will provide 80% power to detect whether these paired differences in the changes from baseline are equal to one standard deviation (SD) of the difference of the changes (effect size=1.0) using a two-tailed 0.05 significance level paired t-test. In practice, a Wilcoxon signed rank test may be used instead of a t-test if the differences are not consistent with a normal distribution (p<0.05 by a Shapiro-Wilks test). ;

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease
• JNS Kinase
• Topical Administration

• NCT number: NCT03395340
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Phase 2
• Start date: November 19, 2018
• Completion date: January 31, 2019