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

NCT03395340 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 18003518-AR-0035
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Graft Versus Host Disease; JNS Kinase; Topical Administration

Keywords

cGVHD; Epidermal; JAK Inhibitor; Skin; JAK-STAT

Outcome Measures

Primary Outcomes (2)

• Percent Change in the Surface Area Measurement of the Target Lesions for Ruxolitinib Treated Versus Placebo Treated Lesions

  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.

  Baseline to week 6

• Number of Participants With Grade 3 and Grade 4 Adverse Events

  Adverse events were measured by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening.

  date on study, up to approximately 2 months and 12 days.

Secondary Outcomes (6)

• Change in Overall Severity Visual Analog Scale (VAS)

  Baseline and week 6

• Change in Pain Visual Analog Scale (VAS)

  Baseline and week 6

• Change in Pruritus Visual Analog Scale (VAS)

  Baseline and week 6

• Area Under the Serum Concentration Versus Time Curve (AUC) of Ruxolitinib

  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.

• Total Clearance (CL) of Ruxolitinib

  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.

Other Outcomes (1)

• Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Date treatment consent signed to date off study, approximately 2 months and 12 days.

Study Arms (2)

Ruxolitinib cream

EXPERIMENTAL

Investigational cream to 1 location; vehicle cream to 2nd location

Drug: Ruxolitinib 1.5% cream

Vehicle cream

PLACEBO COMPARATOR

Investigational cream to 1 location; vehicle cream to 2nd location

Drug: vehicle cream

Interventions

Ruxolitinib 1.5% cream DRUG

Topical formulation of ruxolitinib, a Janus kinases (JAK) 1/2 inhibitor.

Also known as: Opzelura

Ruxolitinib cream

vehicle cream DRUG

Matching vehicle cream applied as a thin film

Vehicle cream

Eligibility Criteria

• Age: 12 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Choi J, Cooper ML, Alahmari B, Ritchey J, Collins L, Holt M, DiPersio JF. Pharmacologic blockade of JAK1/JAK2 reduces GvHD and preserves the graft-versus-leukemia effect. PLoS One. 2014 Oct 7;9(10):e109799. doi: 10.1371/journal.pone.0109799. eCollection 2014.

  PMID: 25289677 BACKGROUND

• Spoerl S, Mathew NR, Bscheider M, Schmitt-Graeff A, Chen S, Mueller T, Verbeek M, Fischer J, Otten V, Schmickl M, Maas-Bauer K, Finke J, Peschel C, Duyster J, Poeck H, Zeiser R, von Bubnoff N. Activity of therapeutic JAK 1/2 blockade in graft-versus-host disease. Blood. 2014 Jun 12;123(24):3832-42. doi: 10.1182/blood-2013-12-543736. Epub 2014 Apr 7.

  PMID: 24711661 BACKGROUND

• Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, Spoerl S, Ditschkowski M, Ecsedi M, Sockel K, Ayuk F, Ajib S, de Fontbrune FS, Na IK, Penter L, Holtick U, Wolf D, Schuler E, Meyer E, Apostolova P, Bertz H, Marks R, Lubbert M, Wasch R, Scheid C, Stolzel F, Ordemann R, Bug G, Kobbe G, Negrin R, Brune M, Spyridonidis A, Schmitt-Graff A, van der Velden W, Huls G, Mielke S, Grigoleit GU, Kuball J, Flynn R, Ihorst G, Du J, Blazar BR, Arnold R, Kroger N, Passweg J, Halter J, Socie G, Beelen D, Peschel C, Neubauer A, Finke J, Duyster J, von Bubnoff N. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015 Oct;29(10):2062-8. doi: 10.1038/leu.2015.212. Epub 2015 Jul 31.

  PMID: 26228813 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Immune System Diseases

Results Point of Contact

• Title: Dr. Edward W. Cowen
• Organization: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

cowene@mail.nih.gov

301-827-2328

Study Officials

• Edward W Cowen, M.D.

  National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: January 10, 2018
• Study Start: November 19, 2018
• Primary Completion: January 31, 2019
• Study Completion: January 31, 2019
• Last Updated: July 12, 2022
• Results First Posted: July 12, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)