Topical Ruxolitinib for Cutaneous Chronic Graft Versus Host Disease (cGVHD)
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|ClinicalTrials.gov Identifier: NCT03395340|
Recruitment Status : Recruiting
First Posted : January 10, 2018
Last Update Posted : September 12, 2019
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.
To test the safety and effectiveness of topical ruxolitinib 1.5 percent cream in people with cGVHD of the skin.
People ages 12 and older with epidermal skin cGVHD
Participants will be screened with:
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.
|Condition or disease||Intervention/treatment||Phase|
|Graft Versus Host Disease JNS Kinase Topical Administration||Drug: Ruxolitinib 1.5% cream Drug: Vehicle cream||Phase 2|
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- 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.
- 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)
- 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%
- Concurrent use of JAK inhibitors (topical or systemic) , fluconazole, or strong CYP3A4 inhibitors
- Known hypersensitivity to JAK inhibitors or their components
- Active infection including CMV, EBV, HIV, HBV, and/or HCV
- Recurrent or progressive malignancy requiring anticancer treatment
- Patients receiving other investigational agents
- 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 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, 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 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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Phase II Study of Topical Ruxolitinib for Cutaneous Chronic Graft Versus Host Disease (cGVHD)|
|Actual Study Start Date :||November 19, 2018|
|Estimated Primary Completion Date :||October 1, 2020|
|Estimated Study Completion Date :||October 1, 2020|
|Experimental: Ruxolitinib Cream||
Drug: Ruxolitinib 1.5% cream
Ruxolitinib cream 1.5% applied as a thin film twice daily (BID)
|Placebo Comparator: Vehicle cream||
Drug: Vehicle cream
Matching vehicle cream applied as a thin film BID
- Counts of the grades of adverse events noted [ Time Frame: continuous ]CTCAE 4 will be used for grade of adverse events and each AE will bedocumented in C3D.
- Surface area measurement [ Time Frame: 6 weeks ]The surface area will be measured by tracing the lesion ontransparency paper and measuring the area from the transparency.
- Pain, pruritus, and overall severity VAS [ Time Frame: 6 weeks ]
- pharmacokinetics [ Time Frame: 2 weeks ]
- pharmacodynamics [ Time Frame: 6 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03395340
|Contact: Michelle O'Brien, R.N.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Dominique C Pichard, M.D.||National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)|