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

October 28, 2021 updated by: Incyte Corporation

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
71

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Expanded Access

Expanded Access

A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the U.S. Food and Drug Administration (FDA). Also called compassionate use. There are different expanded access types.
Approved

Approved

  • Available: Expanded access is currently available for this investigational treatment, and patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied.
  • No longer available: Expanded access was available for this intervention previously but is not currently available and will not be available in the future.
  • Temporarily not available: Expanded access is not currently available for this intervention but is expected to be available in the future.
  • Approved for marketing: The intervention has been approved by the U.S. Food and Drug Administration for use by the public.
 for sale to the public. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
    • California
      • Duarte, California, United States, 31010
      • La Jolla, California, United States, 92903
      • Los Angeles, California, United States, 90095
      • Los Angeles, California, United States, 90033
      • Stanford, California, United States, 94306
    • Colorado
      • Denver, Colorado, United States, 80218
    • Florida
      • Gainesville, Florida, United States, 32610
      • Miami, Florida, United States, 33136
      • Tampa, Florida, United States, 33612
    • Georgia
      • Atlanta, Georgia, United States, 30322
    • Illinois
      • Chicago, Illinois, United States, 60637
      • Chicago, Illinois, United States, 60611
    • Kentucky
      • Lexington, Kentucky, United States, 40536-0293
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
    • Missouri
      • Saint Louis, Missouri, United States, 63110
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
    • New York
      • New York, New York, United States, 10065
      • New York, New York, United States, 10022
      • Rochester, New York, United States, 14642
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
    • Ohio
      • Cincinnati, Ohio, United States, 45242
      • Cleveland, Ohio, United States, 44195
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
      • Philadelphia, Pennsylvania, United States, 19107
      • Pittsburgh, Pennsylvania, United States, 15232
      • Pittsburgh, Pennsylvania, United States, 15224
    • Tennessee
      • Nashville, Tennessee, United States, 37232
      • Nashville, Tennessee, United States, 37203
    • Texas
      • Dallas, Texas, United States, 75246
      • San Antonio, Texas, United States, 78229
    • Utah
      • Salt Lake City, Utah, United States, 84112
    • Washington
      • Seattle, Washington, United States, 98109
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
      • Milwaukee, Wisconsin, United States, 53226

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

8 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: Ruxolitinib
Other Names:
  • Jakafi
  • INCB018424
Drug: Prednisone or methylprednisolone
Either oral prednisone or IV methylprednisolone may be used to begin corticosteroid treatment at the investigator's discretion.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) at Day 28
Time Frame: From baseline to Day 28
Defined as the percentage of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).
From baseline to Day 28

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: From baseline to days 14, 56, and 100
Defined as the percentage of participants demonstrating a CR, VGPR, or PR.
From baseline to days 14, 56, and 100
Nonrelapse Mortality (NRM)
Time Frame: From baseline to Months 6, 9, 12, and 24
Defined as the proportion of subjects who died due to causes other than malignancy relapse.
From baseline to Months 6, 9, 12, and 24
Percentage of Participants With Six-month Duration of Response (DOR)
Time Frame: From Baseline up to 6 months
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.
From Baseline up to 6 months
Percentage of Participants With Three-month DOR
Time Frame: From Baseline up to 3 months
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.
From Baseline up to 3 months
Relapse Rate
Time Frame: From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)
Defined as the percentage of participants whose underlying malignancy relapsed.
From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)
Relapse-related Mortality Rate
Time Frame: From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)
Defined as the percentage of participants whose malignancy relapsed and had a fatal outcome.
From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)
Failure-free Survival (FFS)
Time Frame: From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)
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).
From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)
Overall Survival (OS)
Time Frame: From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)
Defined as the time from study enrollment (first day of ruxolitinib treatment) to death due to any cause.
From Baseline until death, withdrawal of consent, or the end of the study, whichever occurs first (up to approximately 24 months)
Number of Participants With Treatment-emergent Adverse Events (TEAES), Serious TEAEs, And Grade 3 or Higher TEAEs
Time Frame: From signing the informed consent form up to 30-35 days after the last dose of study treatment (up to 24 months)
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.
From signing the informed consent form up to 30-35 days after the last dose of study treatment (up to 24 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Incyte Corporation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Fitzroy Dawkins, MD, Incyte Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 30, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 31, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 14, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 1, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 1, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 3, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 24, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 28, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • INCB 18424-271 (REACH-1)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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