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

NCT ID: NCT02953678

Last Updated: 2021-11-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

71 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-30

Study Completion Date

2019-08-14

Brief Summary

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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).

Detailed Description

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Conditions

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Graft-versus-host Disease (GVHD)

Keywords

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Graft-versus-host disease (GVHD) acute GVHD steroid-refractory ruxolitinib Janus kinase inhibitor

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Ruxolitinib in combination with corticosteroids

Participants 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.

Group Type EXPERIMENTAL

Ruxolitinib

Intervention Type DRUG

Prednisone or methylprednisolone

Intervention Type DRUG

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

Interventions

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Ruxolitinib

Intervention Type DRUG

Prednisone or methylprednisolone

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

Intervention Type DRUG

Other Intervention Names

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Jakafi INCB018424

Eligibility Criteria

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Inclusion Criteria

* 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.
* 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

Exclusion Criteria

* 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.
* 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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fitzroy Dawkins, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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Tucson, Arizona, United States

Site Status

Duarte, California, United States

Site Status

La Jolla, California, United States

Site Status

Los Angeles, California, United States

Site Status

Los Angeles, California, United States

Site Status

Stanford, California, United States

Site Status

Denver, Colorado, United States

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Gainesville, Florida, United States

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Miami, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Lexington, Kentucky, United States

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Boston, Massachusetts, United States

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Grand Rapids, Michigan, United States

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Minneapolis, Minnesota, United States

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St Louis, Missouri, United States

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Hackensack, New Jersey, United States

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New York, New York, United States

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New York, New York, United States

Site Status

Rochester, New York, United States

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Charlotte, North Carolina, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Nashville, Tennessee, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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San Antonio, Texas, United States

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Salt Lake City, Utah, United States

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Seattle, Washington, United States

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Morgantown, West Virginia, United States

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Madison, Wisconsin, United States

Site Status

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 32160294 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29316837 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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INCB 18424-271 (REACH-1)

Identifier Type: -

Identifier Source: org_study_id