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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03395340
Recruitment Status : Terminated (Forced to close study due to poor recruitment (company withdrew drug support).)
First Posted : January 10, 2018
Results First Posted : July 12, 2022
Last Update Posted : July 12, 2022
Sponsor:
Information provided by (Responsible Party):
Edward Cowen, M.D., National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Brief 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.


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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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Phase II Study of Topical Ruxolitinib for Cutaneous Chronic Graft Versus Host Disease (cGVHD)
Actual Study Start Date : November 19, 2018
Actual Primary Completion Date : January 31, 2019
Actual Study Completion Date : January 31, 2019


Arm Intervention/treatment
Experimental: Ruxolitinib cream
Investigational cream to 1 location; vehicle cream to 2nd location
Drug: Ruxolitinib 1.5% cream
Topical formulation of ruxolitinib, a Janus kinases (JAK) 1/2 inhibitor.
Other Name: Opzelura

Placebo Comparator: Vehicle cream
Investigational cream to 1 location; vehicle cream to 2nd location
Drug: vehicle cream
Matching vehicle cream applied as a thin film




Primary Outcome Measures :
  1. Percent Change in the Surface Area Measurement of the Target Lesions for Ruxolitinib Treated Versus Placebo Treated Lesions [ Time Frame: Baseline to week 6 ]
    The surface area will be measured by tracing the lesion on transparency paper and measuring the area from the transparency. Differences in remaining active surface area at 6 weeks from baseline between the treated and placebo sites were compared to calculate efficacy. A decrease in active surface area would signify improvement in skin disease.

  2. Number of Participants With Grade 3 and Grade 4 Adverse Events [ Time Frame: date on study, up to approximately 2 months and 12 days. ]
    Adverse events were measured by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening.


Secondary Outcome Measures :
  1. Change in Overall Severity Visual Analog Scale (VAS) [ Time Frame: Baseline and week 6 ]
    The Overall Severity VAS is a psychometric response questionnaire to measure subjective characteristics or attitudes that cannot be directly measured on a scale of 0-10; a participants assessment of degree of disease activity on the skin. 0=none and 10 = worst imaginable.

  2. Change in Pain Visual Analog Scale (VAS) [ Time Frame: Baseline and week 6 ]
    The Pain VAS is a psychometric response questionnaire to measure subjective characteristics or attitudes that cannot be directly measured on a scale of 0 (no pain) -10 (worst imaginable pain). The participant draws a line on the scale representing how they feel between 0 (none) and 10 (worst). That line is measured and assigned a value. Scores from Baseline and week 6 will be reported. A change is considered a higher number (worsening of disease) or a lower number (improvement of disease) from baseline.

  3. Change in Pruritus Visual Analog Scale (VAS) [ Time Frame: Baseline and week 6 ]
    The pruritus VAS is a psychometric response questionnaire to measure subjective characteristics or attitudes that cannot be directly measured on a scale of 0 (no itching) -10 (worst imaginable itching). Scores from Baseline and week 6 will be reported. A change is considered a higher number (worsening of disease) or a lower number (improvement of disease) from baseline.

  4. Area Under the Serum Concentration Versus Time Curve (AUC) of Ruxolitinib [ Time Frame: A pre-dose trough sample will be collected prior to application of the treatment on the day of the follow up visit. After application in clinic, blood samples will be collected at 1 hour, 2 hour and 4 hours. ]
    The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.

  5. Total Clearance (CL) of Ruxolitinib [ Time Frame: A pre-dose trough sample will be collected prior to application of the treatment on the day of the follow up visit. After application in clinic, blood samples will be collected at 1 hour, 2 hour and 4 hours. ]
    The CL is a quantitative measure of the rate at which a drug substance is removed from the body.

  6. Half-Life of Ruxolitinib [ Time Frame: A pre-dose trough sample will be collected prior to application of the treatment on the day of the follow up visit. After application in clinic, blood samples will be collected at 1 hour, 2 hour and 4 hours. ]
    Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.


Other Outcome Measures:
  1. Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) [ Time Frame: Date treatment consent signed to date off study, approximately 2 months and 12 days. ]
    Here is the number of participants with non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 100 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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


Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
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Principal Investigator: Edward W Cowen, M.D. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  Study Documents (Full-Text)

Documents provided by Edward Cowen, M.D., National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):
Informed Consent Form: Assent  [PDF] March 9, 2021

Additional Information:
Publications:
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Responsible Party: Edward Cowen, M.D., Principal Investigator, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ClinicalTrials.gov Identifier: NCT03395340    
Other Study ID Numbers: 180035
18-AR-0035
First Posted: January 10, 2018    Key Record Dates
Results First Posted: July 12, 2022
Last Update Posted: July 12, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Edward Cowen, M.D., National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):
cGVHD
Epidermal
JAK Inhibitor
Skin
JAK-STAT
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases