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

• Status: Recruiting
• Trial end date: 2024-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Background:

About half the people who have a hematopoietic stem cell transplant using donor cells get 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Criteria

• INCLUSION CRITERIA:

• Patients must have histologically confirmed epidermal cGVHD including lichen planus-like, papulosquamous, and erythematous cGVHD with clinical involvement at 2 separate body regions (e.g. right forearm and left forearm).

• Patients must have measurable disease, defined as at least 2 areas of cutaneous, nonulcerated, epidermal cGVHD involvement. Each site must involve at least 0.5% body surface area (1 palm equivalent) and cannot be a site of current or previous nonmelanoma skin cancer (NMSC).

• Stable immunosuppressant or immunomodulatory systemic cGVHD treatment, including phototherapy and extracorporeal photopheresis, for 4 weeks prior to enrollment.

• Age greater than or equal to 12 years. There is no available safety or adverse events data available for children younger than 12 years of age.

• Karnofsky or Lansky greater than or equal to 60

• Patients must have normal organ and marrow function as defined below:

• absolute neutrophil count greater than or equal to 1,000/mcL

• platelets greater than or equal to 50,000/mcL

• hemoglobin > 9 g/dL

• total bilirubin <1.5X institutional upper limit of normal except if known history of Gilbert's disease

• AST(SGOT)/ALT(SGPT) less than or equal to 5X institutional upper limit of normal

• creatinine clearance greater than or equal to 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

• Willingness to comply with twice daily application of 2 different creams to 2 separate, prespecified sites.

• The effects of ruxolitinib on the developing human fetus are unknown. For this reason, 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.

• Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

• Patients concurrently receiving a JAK inhibitor (topical or systemic).

• Patients receiving any other investigational agents.

• Patients concurrently taking oral fluconazole.

• Patients concurrently taking strong CYP3A4 inhibitors.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib or other agents used in study.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection including EBV, CMV, HIV, HBV, and HCV, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant women are excluded from this study because ruxolitinib is an agent with the potential for teratogenic or abortifacient effects. Because there is 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. These potential risks may also apply to other agents used in this study.

• Recurrent or progressive malignancy requiring anticancer treatment.

• Other cancer (except that for which HCT was performed) within 2 years of study entry, except nonmelanoma skin cancer or carcinoma in situ of the breast, uterus, or cervix.

• History of cutaneous malignancy at target lesion site.

• Any participant who, in the investigator s opinion, would be unable to comply with study requirements or for whom participation may pose a greater medical risk.