Graft-versus-host-disease (GVHD)Phase 2NCT03616184
Study of Ruxolitinib in Sclerotic Chronic Graft-Versus-Host Disease After Failure of Systemic Glucocorticoids
A Phase 2 study testing Ruxolitinib in people with Graft-versus-host-disease (GVHD), run by University of Nebraska at 5 sites in United States.
Trial summary
The primary objective of the study is to examine the efficacy of ruxolitinib in patients with sclerotic chronic graft-versus-host disease (GVHD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft-versus-host-disease (GVHD)
- What is being tested?
- Ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 5 sitesUnited States
- Study dates
- 5 Sep 2018to 12 Jun 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Sclerotic chronic GVHD (classic chronic or overlap syndrome) that meets 2014 NIH Consensus Criteria. Eligible patients will have superficial or deep skin sclerosis, fasciitis or joint contractures.
- The subject must have received the following therapy for chronic GVHD (not necessarily for sclerotic manifestations): A - Systemic corticosteroids for >12 months and at least one additional line of systemic therapy OR B - Systemic corticosteroids and at least two additional lines of systemic therapy. For the purpose of this study, fluticasone, azithromycin and montelukast ("FAM") therapy for lung GVHD will be considered a topical therapy. Investigators are encouraged but not mandated to use ibrutinib for appropriate patients prior to enrollment in this trial.
- Adults, Age ≥18 years (state of Nebraska, Age ≥19 years)
- Karnofsky performance status ≥60% at the time of enrollment
- All allogeneic donor sources and all conditioning regimens are allowed.
- Absolute neutrophil count (ANC) greater than 1000/µL, and platelet count ³50,000/µL without the use of growth factors or platelet transfusion.
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- Able to take orally-administered medication.
- Female patient of reproductive potential must have a negative serum or urine pregnancy test ≤7 days prior to starting the study drug. Women are considered NOT to have reproductive potential if they have had 12 months of amenorrhea with an appropriate clinical profile (i.e. ≥51 years, history of vasomotor symptoms, OR supportive hormone levels such as low estrogen and high follicle-stimulating hormone levels), OR surgical sterilization.
- Male and female patients of reproductive potential must be willing to avoid pregnancy or fathering children from enrollment to one month after the end of study treatment. This will require either a total abstinence, OR exclusively non-heterosexual activity (when this is in line with the preferred and usual lifestyle of the subject), OR two methods of contraception (male or female condom with or without a spermicidal agent, diaphragm or cervical cap with spermicide, or hormonal based contraception including intrauterine device).
- Life expectancy greater than 6 months
- Written informed consent to participate in the study.
Who cannot join
- Fibrosis of internal organs such as gut, liver or lung as the sole manifestation of sclerosis.
- Fluconazole at a dose more than 200 mg daily. Patients should stop fluconazole or lower dose to less than or equal to 200 mg daily before starting ruxolitinib.
- Current evidence of malignancy after allogeneic transplant.
- History of progressive multifocal leuko-encephalopathy (PML)
- Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection
- Presence of known HIV infection, active hepatitis B or C infection.
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- Active tuberculosis infection that developed after allogeneic hematopoietic cell transplant (HCT)
- Total bilirubin 1.5 ´ the upper limit of the normal range
- Creatinine clearance <30 mL/min
- 10. Presence of uncontrolled cardiopulmonary conditions such as ongoing cardiac arrhythmias, unstable angina or myocardial infarction, uncontrolled hypertension (e.g. blood pressure higher than 150/90 for patients 60 years or older, or higher than 140/90 for patients younger than 60 years, or those with diabetes and chronic kidney disease), New York Heart Association class III/IV congestive heart failure, or requirement of supplemental oxygen at rest or having a resting O2 saturation <90% by pulse oximetry.
- Any other condition that is judged by the physician to potentially interfere with compliance to the study protocol or pose a significant risk to the patient.
- Pregnancy, breastfeeding or planning to be pregnant.
- Exposure to Janus kinase inhibitors (JAK) inhibitor therapy for any indication after allogeneic transplant
- Initiation of a new systemic immunosuppressant for management of chronic GVHD within 8 weeks prior to enrollment. However, patients who develop disease progression can enroll as early as 4 weeks after initiation of a new systemic immunosuppressant. Also, patients who are unable to tolerate current therapy can enroll any time after initiation of a new systemic immunosuppressant, as long as the "new" immunosuppressant is stopped in these cases prior to initiation of ruxolitinib. Initiation of any new topical therapy (including FAM or intra-oral narrow-band UVB phototherapy) and changes in dose of existing immunosuppressive agents such as corticosteroids, sirolimus, calcineurin inhibitors or other agents are acceptable at any time prior to enrollment. The use of immunosuppressants for short term period, for example 7 days, for indications other than GVHD will be acceptable.
- Treatment with any other investigational agent, device, or procedure, within 21 days (or 5 half-lives, whichever is greater)
- Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Cleveland Clinic
Cleveland, Ohio, 44195
Ohio State University
Columbus, Ohio, 43210
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: A Single Arm, Open Label, Phase II Study of Ruxolitinib in Sclerotic Chronic Graft-Versus-Host Disease After Failure of Systemic Glucocorticoids
The primary objective of the study is to examine the efficacy of ruxolitinib in patients with sclerotic chronic graft-versus-host disease (GVHD).
Read the detailed description
Chronic graft-versus-host-disease (GVHD) is a major complication of allogeneic hematopoietic cell transplant that impairs quality of life, and is associated with significant morbidity and mortality. Management of chronic GVHD with prednisone is associated with an overall response rate of approximately 60%, and a complete response rate of approximately 30% but sclerotic features do not respond as well. Based on the biology of chronic GVHD and available preliminary evidence, the investigators hypothesize that ruxolitinib will be effective in the management of sclerotic chronic GVHD. The study is an open label, phase II multicenter trial designed to evaluate the efficacy of ruxolitinib as a salvage treatment for patients with sclerotic GVHD (sclerosis or fasciitis). The primary objective is to determine the proportion of patients with response rate (complete and partial responses) in skin and/or joint, as determined by 2014 NIH (National Institutes of Health) consensus criteria, at 6 months of therapy with ruxolitinib. Eligibility criteria includes adult patients with chronic GVHD and skin, joint and/or fascia sclerosis, who have received systemic corticosteroids for >12 months and at least one additional line of therapy OR systemic corticosteroids and at least two additional lines of therapy for chronic GVHD. A sample size of 47 patients (43 evaluable patients and estimated 10% dropout) will allow an α of 0.044 and a power of 84% to test the null hypothesis response rate of 25% compared to an alternative of 45%. Subjects will receive ruxolitinib for 6 months for the treatment of sclerotic chronic GVHD. Subjects will be evaluated for GVHD status as well as non-relapse mortality, relapse of underlying malignancy and quality of life/functional status. Plasma cytokine levels and T/Natural Killer (NK) cell subset in peripheral blood will be measured at various time points. The response rate will be reported as a proportion and 95% exact confidence interval. If positive, the trial results will support other ongoing studies to establish the role of ruxolitinib in chronic GVHD in general and specifically in sclerotic chronic GVHD.
- Conditions
- Graft-versus-host-disease (GVHD)
- Being tested
- Ruxolitinib
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
Patients with sclerotic chronic graft-versus-host disease (GVHD) will receive oral ruxolitinib at a dose of 10 mg twice daily. Doses may not exceed 10 mg twice daily. Ruxolitinib will be continued for 6 months. Patients who continue to have stable disease, mixed responses or partial/complete responses at the end of 6 months may continue the drug for a total of 12 months.
| Study group | Role | What they receive |
|---|---|---|
| Ruxolitinib | Experimental | Patients will receive oral ruxolitinib at a dose of 10 mg twice daily. Receives: Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Complete and Partial Responses in Skin and/or Joint
The primary endpoint of the study was complete or partial response in skin and/or joint defined according to the 2014 NIH cGVHD Consensus Criteria. Partial response for skin would be a decrease in NIH Skin Score by 1 or more points. Partial response in joint would be a decrease in NIH Joint and Fascia Score by 1 or more points or increase in P-ROM score by 1 point for any site.
Measured: 6 months
Secondary outcomes (1)
Percentage of Participants With Complete or Partial Responses Overall
As determined by 2014 NIH Criteria which is a clinician overall severity score of 0 for complete response and clinician overall severity score decreased by 2 or more points on a 0-10 scale for partial response.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2018
- Study start5 Sep 2018
- Primary completion22 Jan 2022
- Study completion12 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Graft-versus-host-disease (GVHD)Studies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vijaya Bhatt, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03616184
- Sponsor's protocol ID
- 0333-18-FB
- Status last verified
- Sep 2023
- First submitted
- 29 Jul 2018
- Last updated
- 5 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bhatt VR, Shostrom VK, Choe HK, Hamilton BK, Gundabolu K, Maness LJ, Kumar V, Mahato RI, Smith LM, Nishihori T, Lee SJ. A Multicenter Phase II Trial of Ruxolitinib for Treatment of Corticosteroid Refractory Sclerotic Chronic Graft-Versus-Host Disease. J Clin Oncol. 2024 Nov 20;42(33):3977-3985. doi: 10.1200/JCO.24.00205. Epub 2024 Aug 16.
PubMed 39151112
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Open Label, Phase II Study of Ruxolitinib in Sclerotic Chronic Graft-Versus-Host Disease After Failure of Systemic Glucocorticoids
- ClinicalTrials.gov ID
- NCT03616184
- Acronym / sponsor ID
- 0333-18-FB
- Conditions
- Graft-versus-host-disease (GVHD)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 5 Sep 2018 (actual)
- Primary completion
- 22 Jan 2022 (actual)
- Study completion
- 12 Jun 2023 (actual)
- First posted
- 6 Aug 2018 (actual)
- Results
- Posted 14 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the study is to examine the efficacy of ruxolitinib in patients with sclerotic chronic graft-versus-host disease (GVHD).
Detailed description
Chronic graft-versus-host-disease (GVHD) is a major complication of allogeneic hematopoietic cell transplant that impairs quality of life, and is associated with significant morbidity and mortality. Management of chronic GVHD with prednisone is associated with an overall response rate of approximately 60%, and a complete response rate of approximately 30% but sclerotic features do not respond as well. Based on the biology of chronic GVHD and available preliminary evidence, the investigators hypothesize that ruxolitinib will be effective in the management of sclerotic chronic GVHD. The study is an open label, phase II multicenter trial designed to evaluate the efficacy of ruxolitinib as a salvage treatment for patients with sclerotic GVHD (sclerosis or fasciitis). The primary objective is to determine the proportion of patients with response rate (complete and partial responses) in skin and/or joint, as determined by 2014 NIH (National Institutes of Health) consensus criteria, at 6 months of therapy with ruxolitinib. Eligibility criteria includes adult patients with chronic GVHD and skin, joint and/or fascia sclerosis, who have received systemic corticosteroids for >12 months and at least one additional line of therapy OR systemic corticosteroids and at least two additional lines of therapy for chronic GVHD. A sample size of 47 patients (43 evaluable patients and estimated 10% dropout) will allow an α of 0.044 and a power of 84% to test the null hypothesis response rate of 25% compared to an alternative of 45%. Subjects will receive ruxolitinib for 6 months for the treatment of sclerotic chronic GVHD. Subjects will be evaluated for GVHD status as well as non-relapse mortality, relapse of underlying malignancy and quality of life/functional status. Plasma cytokine levels and T/Natural Killer (NK) cell subset in peripheral blood will be measured at various time points. The response rate will be reported as a proportion and 95% exact confidence interval. If positive, the trial results will support other ongoing studies to establish the role of ruxolitinib in chronic GVHD in general and specifically in sclerotic chronic GVHD.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ruxolitinib | Experimental | Drug: RuxolitinibPatients will receive oral ruxolitinib at a dose of 10 mg twice daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Sclerotic chronic GVHD (classic chronic or overlap syndrome) that meets 2014 NIH Consensus Criteria. Eligible patients will have superficial or deep skin sclerosis, fasciitis or joint contractures.
- The subject must have received the following therapy for chronic GVHD (not necessarily for sclerotic manifestations): A - Systemic corticosteroids for >12 months and at least one additional line of systemic therapy OR B - Systemic corticosteroids and at least two additional lines of systemic therapy. For the purpose of this study, fluticasone, azithromycin and montelukast ("FAM") therapy for lung GVHD will be considered a topical therapy. Investigators are encouraged but not mandated to use ibrutinib for appropriate patients prior to enrollment in this trial.
- Adults, Age ≥18 years (state of Nebraska, Age ≥19 years)
- Karnofsky performance status ≥60% at the time of enrollment
- All allogeneic donor sources and all conditioning regimens are allowed.
Key exclusion criteria (16 listed)
- Fibrosis of internal organs such as gut, liver or lung as the sole manifestation of sclerosis.
- Fluconazole at a dose more than 200 mg daily. Patients should stop fluconazole or lower dose to less than or equal to 200 mg daily before starting ruxolitinib.
- Current evidence of malignancy after allogeneic transplant.
- History of progressive multifocal leuko-encephalopathy (PML)
- Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RuxolitinibPatients with sclerotic chronic graft-versus-host disease (GVHD) will receive oral ruxolitinib at a dose of 10 mg twice daily. Doses may not exceed 10 mg twice daily. Ruxolitinib will be continued for 6 months. Patients who continue to have stable disease, mixed responses or partial/complete responses at the end of 6 months may continue the drug for a total of 12 months. | Drug | Ruxolitinib |
Primary outcome
Percentage of Participants With Complete and Partial Responses in Skin and/or Joint
Time frame: 6 months
The primary endpoint of the study was complete or partial response in skin and/or joint defined according to the 2014 NIH cGVHD Consensus Criteria. Partial response for skin would be a decrease in NIH Skin Score by 1 or more points. Partial response in joint would be a decrease in NIH Joint and Fascia Score by 1 or more points or increase in P-ROM score by 1 point for any site.
1 secondary outcome
Percentage of Participants With Complete or Partial Responses Overall
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39151112Bhatt VR, Shostrom VK, Choe HK, Hamilton BK, Gundabolu K, Maness LJ, Kumar V, Mahato RI, Smith LM, Nishihori T, Lee SJ. A Multicenter Phase II Trial of Ruxolitinib for Treatment of Corticosteroid Refractory Sclerotic Chronic Graft-Versus-Host Disease. J Clin Oncol. 2024 Nov 20;42(33):3977-3985. doi: 10.1200/JCO.24.00205. Epub 2024 Aug 16.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vijaya Bhatt, MD principal investigator
University of Nebraska
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ruxolitinib in people with Graft-versus-host-disease (GVHD), run by University of Nebraska at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Complete and Partial Responses in Skin and/or Joint (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03616184, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2023.