Topical Ruxolitinib for Cutaneous Chronic Graft Versus Host Disease (cGVHD)
Condition: Graft Versus Host Disease; JNS Kinase; Topical Administration
MeSH terms: Bronchiolitis Obliterans Syndrome; Graft vs Host Disease
Intervention: Ruxolitinib 1.5% cream; vehicle cream
Intervention description: Topical formulation of ruxolitinib, a Janus kinases (JAK) 1/2 inhibitor.; Matching vehicle cream applied as a thin film
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 1.0
Sex: All
Minimum age: 12 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: cGVHD; Epidermal; JAK Inhibitor; Skin; JAK-STAT

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Patients must have histologically confirmed epidermal Chronic Graft Versus Host
             Disease (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

               -  Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase
                  (SGOT)/alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT)
                  less than or equal to 5X institutional upper limit of normal

               -  creatinine clearance greater than or equal to 50 mL/min/1.73 m^2 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 Janus kinase (JAK) inhibitor (topical or systemic).

          -  Patients receiving any other investigational agents.

          -  Patients concurrently taking oral fluconazole.

          -  Patients concurrently taking strong Cytochrome P450 3A4 (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 Epstein-Barr virus (EBV), Cytomegalovirus (CMV), human
             immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (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 hematopoietic cell transplantation (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.