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Graft-versus-host Disease (GVHD)Phase 2NCT02953678

A Study of Ruxolitinib in Combination With Corticosteroids for the Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease (REACH-1)

A Phase 2 study testing Ruxolitinib and Prednisone or methylprednisolone in people with Graft-versus-host Disease (GVHD), run by Incyte Corporation at 38 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study was to assess the efficacy of ruxolitinib in combination with corticosteroids in subjects with Grades II to IV steroid-refractory acute graft-versus-host disease (GVHD). Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Graft-versus-host Disease (GVHD)
What is being tested?
Ruxolitinib and Prednisone or methylprednisolone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
71 participants
Where
38 sitesUnited States
Study dates
30 Dec 2016to 14 Aug 2019
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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Have undergone first allogeneic hematopoietic stem cell transplantation (allo-HSCT) from any donor source using bone marrow, peripheral blood stem cells, or cord blood for hematologic malignancies. Recipients of nonmyeloablative and myeloablative conditioning regimens are eligible.
  • Clinically suspected Grades II to IV acute GVHD as per MAGIC guidelines, occurring after allo-HSCT with any conditioning regimen and any anti-GVHD prophylactic program.
  • Subjects with steroid-refractory acute GVHD, defined as any of the following:
  • Subjects with progressive GVHD (ie, increase in stage in any organ system or any new organ involvement) after 3 days of primary treatment with methylprednisolone ≥ 2 mg/kg per day (or equivalent).
  • Subjects with GVHD that has not improved (ie, decrease in stage in at least 1 involved organ system) after 7 days of primary treatment with methylprednisolone ≥ 2 mg/kg per day (or equivalent).
  • Subjects who previously began corticosteroid therapy at a lower dose (at least 1 mg/kg per day methylprednisolone) but develop new GVHD in another organ system.
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  • Subjects who cannot tolerate a corticosteroid taper, that is, begin corticosteroids at 2.0 mg/kg per day, demonstrate response, but progress before a 50% decrease from the initial starting dose of corticosteroids is achieved.
  • Evidence of myeloid engraftment (eg, absolute neutrophil count ≥ 0.5 × 10^9/L for 3 consecutive days if ablative therapy was previously used). Use of growth factor supplementation is allowed.
  • Be willing to avoid pregnancy or fathering children

Who cannot join

  • Has received more than 1 allo-HSCT.
  • Has received more than 1 systemic treatment in addition to corticosteroids for acute GVHD.
  • Presence of GVHD overlap syndrome as per NIH guidelines.
  • Subjects who have had a splenectomy.
  • Presence of an active uncontrolled infection. An active uncontrolled infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without signs or symptoms will not be interpreted as an active uncontrolled infection.
  • Known human immunodeficiency virus infection.
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  • Active hepatitis B virus (HBV) or hepatitis C virus infection that requires treatment or at risk for HBV reactivation. Subjects whose immune status is unknown or uncertain must have results confirming immune status before enrollment.
  • Serum creatinine > 2.0 mg/dL or creatinine clearance < 40 mL/min measured or calculated by Cockcroft-Gault equation.
  • Subjects with evidence of relapsed primary disease, or subjects who have been treated for relapse after the allo-HSCT was performed.
  • Unresolved toxicity or complications (other than acute GVHD) due to previous allo-HSCT.
  • Any corticosteroid therapy for indications other than GVHD at doses of methylprednisolone or equivalent > 1 mg/kg per day within 7 days of enrollment.
  • Severe organ dysfunction unrelated to underlying GVHD, including:
  • Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GVHD and ongoing organ dysfunction).
  • Clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that requires therapy.
  • Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
  • Currently breast feeding.
  • Received Janus kinase inhibitor (JAK) therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted.
  • Treatment with any other investigational agent, device, or procedure, within 21 days (or 5 half-lives, whichever is greater) of enrollment. Subjects participating in a GVHD prophylaxis study or conditioning regimen should be discussed with the sponsor's medical monitor before enrollment.
  • Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
  • Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.

Trial locations and contacts

38 sites in 1 country.

38 sites in 1 country

United States38 sites

  • Study site

    Atlanta, Georgia, 30322

  • Study site

    Boston, Massachusetts, 02114

  • Study site

    Charlotte, North Carolina, 28204

  • Study site

    Chicago, Illinois, 60611

  • Study site

    Chicago, Illinois, 60637

  • Study site

    Cincinnati, Ohio, 45242

  • Study site

    Cleveland, Ohio, 44195

  • Study site

    Dallas, Texas, 75246

  • Study site

    Denver, Colorado, 80218

  • Study site

    Duarte, California, 31010

  • Study site

    Gainesville, Florida, 32610

  • Study site

    Grand Rapids, Michigan, 49503

  • Study site

    Hackensack, New Jersey, 07601

  • Study site

    La Jolla, California, 92903

  • Study site

    Lexington, Kentucky, 40536-0293

  • Study site

    Los Angeles, California, 90033

  • Study site

    Los Angeles, California, 90095

  • Study site

    Madison, Wisconsin, 53705

  • Study site

    Miami, Florida, 33136

  • Study site

    Milwaukee, Wisconsin, 53226

  • Study site

    Minneapolis, Minnesota, 55455

  • Study site

    Morgantown, West Virginia, 26506

  • Study site

    Nashville, Tennessee, 37203

  • Study site

    Nashville, Tennessee, 37232

  • Study site

    New York, New York, 10022

  • Study site

    New York, New York, 10065

  • Study site

    Philadelphia, Pennsylvania, 19104

  • Study site

    Philadelphia, Pennsylvania, 19107

  • Study site

    Pittsburgh, Pennsylvania, 15224

  • Study site

    Pittsburgh, Pennsylvania, 15232

  • Study site

    Rochester, New York, 14642

  • Study site

    Salt Lake City, Utah, 84112

  • Study site

    San Antonio, Texas, 78229

  • Study site

    Seattle, Washington, 98109

  • Study site

    St Louis, Missouri, 63110

  • Study site

    Stanford, California, 94306

  • Study site

    Tampa, Florida, 33612

  • Study site

    Tucson, Arizona, 85719

Other trials in United States

About this study

Official title: A Single-Cohort, Phase 2 Study of Ruxolitinib in Combination With Corticosteroids for the Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease (REACH-1)

The purpose of this study was to assess the efficacy of ruxolitinib in combination with corticosteroids in subjects with Grades II to IV steroid-refractory acute graft-versus-host disease (GVHD).

Being tested
Ruxolitinib, Prednisone or methylprednisolone
Keywords
Graft-versus-host disease (GVHD), acute GVHD, steroid-refractory, ruxolitinib, Janus kinase inhibitor
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

    Also called Jakafi, INCB018424

  • Prednisone or methylprednisoloneDrug

    Either oral prednisone or IV methylprednisolone may be used to begin corticosteroid treatment at the investigator's discretion.

Study groups in NCT02953678
Study groupRoleWhat they receive
Ruxolitinib in combination with corticosteroidsExperimentalParticipants began oral administration of ruxolitinib at 5 mg twice daily (BID); if stable after the first 3 days of treatment, the dose could be increased to 10 mg BID.
Receives: Drug: Ruxolitinib; Drug: Prednisone or methylprednisolone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR) at Day 28

    Defined as the percentage of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).

    Measured: From baseline to Day 28

Secondary outcomes (9)

  1. Overall Response Rate (ORR)

    Defined as the percentage of participants demonstrating a CR, VGPR, or PR.

    Measured: From baseline to days 14, 56, and 100

  2. Nonrelapse Mortality (NRM)

    Defined as the proportion of subjects who died due to causes other than malignancy relapse.

    Measured: From baseline to Months 6, 9, 12, and 24

  3. Percentage of Participants With Six-month Duration of Response (DOR)

    Defined as the time from first response until graft-versus-host disease (GVHD) progression or death. DOR was assessed when all participants who were on the study completed the Day 180 visit.

    Measured: From Baseline up to 6 months

  4. Percentage of Participants With Three-month DOR

    Defined as the time from first response until GVHD progression or death. DOR was assessed when all participants who were on the study completed the Day 84 visit.

    Measured: From Baseline up to 3 months

  5. Relapse Rate

    Defined as the percentage of participants whose underlying malignancy relapsed.

    Measured: From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)

  6. Relapse-related Mortality Rate

    Defined as the percentage of participants whose malignancy relapsed and had a fatal outcome.

    Measured: From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)

  7. Failure-free Survival (FFS)

    Defined as the time from first dose of ruxolitinib to the earliest date that a participant died, had a relapse/progression of the underlying malignancy, required additional therapy for aGVHD, or demonstrated signs or symptoms of chronic graft-versus-host disease (cGVHD).

    Measured: From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)

  8. Overall Survival (OS)

    Defined as the time from study enrollment (first day of ruxolitinib treatment) to death due to any cause.

    Measured: From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)

  9. Number of Participants With Treatment-emergent Adverse Events (TEAES), Serious TEAEs, And Grade 3 or Higher TEAEs

    AE was any unfavorable and unintended sign, symptom, or disease temporally associated with use of medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. Serious AE was any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization. TEAE was an AE that was reported for the first time, or worsening of a pre-existing event after the first dose of study drug (until 30 days after the last dose of study drug). Severity of AEs was described and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03). Grade 3 and above would constitute a severe, life-threatening, or death event.

    Measured: From signing the informed consent form up to 30-35 days after the last dose of study treatment (up to 24 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Nov 2016 (estimated)
  2. Study start30 Dec 2016
  3. Primary completion31 Jan 2018
  4. Study completion14 Aug 2019

Resources

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
71 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02953678
Sponsor's protocol ID
INCB 18424-271 (REACH-1)
Status last verified
Oct 2021
First submitted
1 Nov 2016
Last updated
24 Nov 2021
Data monitoring committee
No
Expanded access
Available

Publications

  • Jagasia M, Perales MA, Schroeder MA, Ali H, Shah NN, Chen YB, Fazal S, Dawkins FW, Arbushites MC, Tian C, Connelly-Smith L, Howell MD, Khoury HJ. Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood. 2020 May 14;135(20):1739-1749. doi: 10.1182/blood.2020004823.

    PubMed 32160294

  • Jagasia M, Zeiser R, Arbushites M, Delaite P, Gadbaw B, Bubnoff NV. Ruxolitinib for the treatment of patients with steroid-refractory GVHD: an introduction to the REACH trials. Immunotherapy. 2018 Apr;10(5):391-402. doi: 10.2217/imt-2017-0156. Epub 2018 Jan 10.

    PubMed 29316837

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ruxolitinib and Prednisone or methylprednisolone in people with Graft-versus-host Disease (GVHD), run by Incyte Corporation at 38 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 9 inclusion and 20 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 24 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 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 20 Aug 2019). 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?

Overall Response Rate (ORR) at Day 28 (time frame: From baseline to Day 28). 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 NCT02953678, which also lists 2 linked publications.

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 24 Nov 2021.

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