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

NCT02953678 | Completed Phase 2 Results

• 1 other identifier: INCB 18424-271 (REACH-1)
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 38

Brief 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).

Conditions

Graft-versus-host Disease (GVHD)

Keywords

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

Outcome Measures

Primary Outcomes (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).

  From baseline to Day 28

Secondary Outcomes (9)

• Overall Response Rate (ORR)

  From baseline to days 14, 56, and 100

• Nonrelapse Mortality (NRM)

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

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

  From Baseline up to 6 months

• Percentage of Participants With Three-month DOR

  From Baseline up to 3 months

• Relapse Rate

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

Study Arms (1)

Ruxolitinib in combination with corticosteroids

EXPERIMENTAL

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; Drug: Prednisone or methylprednisolone

Interventions

Ruxolitinib DRUG

Also known as: Jakafi, INCB018424

Ruxolitinib in combination with corticosteroids

Prednisone or methylprednisolone DRUG

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

Ruxolitinib in combination with corticosteroids

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (38)

Unknown Facility

Tucson, Arizona, 85719, United States

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Duarte, California, 31010, United States

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La Jolla, California, 92903, United States

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Los Angeles, California, 90033, United States

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Los Angeles, California, 90095, United States

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Stanford, California, 94306, United States

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Denver, Colorado, 80218, United States

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Gainesville, Florida, 32610, United States

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Miami, Florida, 33136, United States

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Tampa, Florida, 33612, United States

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Atlanta, Georgia, 30322, United States

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Chicago, Illinois, 60611, United States

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Chicago, Illinois, 60637, United States

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Lexington, Kentucky, 40536-0293, United States

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Boston, Massachusetts, 02114, United States

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Grand Rapids, Michigan, 49503, United States

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Minneapolis, Minnesota, 55455, United States

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St Louis, Missouri, 63110, United States

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Hackensack, New Jersey, 07601, United States

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New York, New York, 10022, United States

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New York, New York, 10065, United States

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Rochester, New York, 14642, United States

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Charlotte, North Carolina, 28204, United States

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Cincinnati, Ohio, 45242, United States

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Cleveland, Ohio, 44195, United States

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Philadelphia, Pennsylvania, 19104, United States

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Philadelphia, Pennsylvania, 19107, United States

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Pittsburgh, Pennsylvania, 15224, United States

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Pittsburgh, Pennsylvania, 15232, United States

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Nashville, Tennessee, 37203, United States

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Nashville, Tennessee, 37232, United States

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Dallas, Texas, 75246, United States

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San Antonio, Texas, 78229, United States

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Salt Lake City, Utah, 84112, United States

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Seattle, Washington, 98109, United States

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Morgantown, West Virginia, 26506, United States

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Madison, Wisconsin, 53705, United States

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Unknown Facility

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• 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.

  PMID: 32160294 DERIVED

• 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.

  PMID: 29316837 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

ruxolitinib; Prednisone; Methylprednisolone

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Prednisolone; Pregnadienetriols

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Fitzroy Dawkins, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: November 1, 2016
• First Posted: November 3, 2016
• Study Start: December 30, 2016
• Primary Completion: January 31, 2018
• Study Completion: August 14, 2019
• Last Updated: November 24, 2021
• Results First Posted: August 20, 2019

Record last verified: 2021-10

Locations

US (38)