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A Study of Ruxolitinib in Combination With Corticosteroids for the Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease (REACH1)

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ClinicalTrials.gov Identifier: NCT02953678
Recruitment Status : Active, not recruiting
First Posted : November 3, 2016
Last Update Posted : February 1, 2019
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Brief Summary:
The purpose of this study is 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).

Condition or disease Intervention/treatment Phase
Graft-versus-host Disease (GVHD) Drug: Ruxolitinib Drug: Prednisone or methylprednisolone Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 71 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 (REACH1)
Actual Study Start Date : December 27, 2016
Actual Primary Completion Date : February 4, 2018
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
Experimental: Ruxolitinib in combination with corticosteroids
Participants began oral administration of ruxolitinib at 5 mg 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.




Primary Outcome Measures :
  1. Overall response rate (ORR) at Day 28 [ Time Frame: From baseline to Day 28 ]
    Defined as the proportion of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).


Secondary Outcome Measures :
  1. Six-month duration of response (DOR) [ Time Frame: From baseline to Day 180 ]
    Defined as the time from first response until graft-versus-host disease (GVHD) progression or death. DOR will be assessed when all participants who are still on study complete the Day 180 visit.

  2. Overall response rate (ORR) [ Time Frame: From baseline to days 14, 56, and 100 ]
    Defined as the proportion of participants demonstrating a CR, VGPR, or PR.

  3. Duration of response (DOR) [ Time Frame: baseline to Day 84 ]
    Defined as the time from first response until GVHD progression or death, when all participants who are still on study complete the Day 84 visit.

  4. 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.

  5. Relapse rate [ Time Frame: From baseline to Day 84 ]
    Defined as the proportion of participants whose underlying malignancy relapsed.

  6. Relapse-related mortality rate [ Time Frame: From baseline to Day 84 ]
    Defined as the proportion of participants whose malignancy relapsed and had a fatal outcome.

  7. Failure-free survival (FFS) [ Time Frame: From baseline to Day 84 ]
    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).

  8. Overall survival (OS) [ Time Frame: From baseline to Day 84 ]
    Defined as the time from study enrollment (first day of ruxolitinib treatment) to death due to any cause.

  9. Incidence and severity of adverse events [ Time Frame: From baseline to 30-35 days after end of treatment, up to 24 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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.
  • 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 Cockroft-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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02953678


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Sponsors and Collaborators
Incyte Corporation
Investigators
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Study Director: Fitzroy Dawkins, MD Incyte Corporation

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT02953678     History of Changes
Other Study ID Numbers: INCB 18424-271 (REACH1)
First Posted: November 3, 2016    Key Record Dates
Last Update Posted: February 1, 2019
Last Verified: January 2019

Keywords provided by Incyte Corporation:
Graft-versus-host disease (GVHD)
acute GVHD
steroid-refractory
ruxolitinib
Janus kinase inhibitor

Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Prednisone
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents