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GRAVITAS-309: Itacitinib or Placebo in Combination With Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease

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ClinicalTrials.gov Identifier: NCT03584516
Recruitment Status : Recruiting
First Posted : July 12, 2018
Last Update Posted : April 24, 2019
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Brief Summary:
The purpose of this study is to assess the efficacy and safety of itacitinib in combination with corticosteroids as first-line treatment for moderate or severe chronic graft-versus-host disease (cGVHD).

Condition or disease Intervention/treatment Phase
Chronic Graft-versus-host Disease Drug: Itacitinib Drug: Placebo Drug: Methylprednisolone Drug: Prednisone Phase 3

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)
Estimated Enrollment : 266 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: In Part 2 of the study, participants in the placebo group will be allowed to cross over to the experimental group after completion of the primary analysis.
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: GRAVITAS-309: A Phase 3 Study of Itacitinib or Placebo in Combination With Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
Actual Study Start Date : January 17, 2019
Estimated Primary Completion Date : August 17, 2023
Estimated Study Completion Date : October 17, 2023


Arm Intervention/treatment
Experimental: Itacitinib + corticosteroids
Itacitinib administered in combination with corticosteroids.
Drug: Itacitinib
In Part 1 participants will receive itacitinib administered orally once daily at the protocol-defined dose according to cohort enrollment. In Part 2, participants will receive the recommended dose from Part 1.
Other Name: INCB039110

Drug: Methylprednisolone
Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.
Other Name: Medrol, Medrol Dosepak, Solu-Medrol

Drug: Prednisone
Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.
Other Name: Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS

Placebo Comparator: Placebo + corticosteroids
Placebo administered in combination with corticosteroids.
Drug: Placebo
In Part 2, participants will receive matching placebo.

Drug: Methylprednisolone
Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.
Other Name: Medrol, Medrol Dosepak, Solu-Medrol

Drug: Prednisone
Administered in Parts 1 and 2 as background reference therapy at a dose level that is commensurate with institutional guidelines based on organ involvement and severity of disease.
Other Name: Deltasone, Prednicot, predniSONE Intensol, Rayos, Sterapred, Sterapred DS




Primary Outcome Measures :
  1. Part 1: Number of dose-limiting toxicities [ Time Frame: 28 days ]
    To identify an appropriate dose of itacitinib in combination with corticosteroids as initial treatment for moderate or severe cGVHD.

  2. Part 2: Response rate [ Time Frame: Month 6 ]
    Defined as the proportion of participants demonstrating a complete response (CR) or partial response (PR) per National Institutes of Health (NIH) consensus guideline.


Secondary Outcome Measures :
  1. Part 1 and Part 2: Cmax of itacitinib when administered in combination with corticosteroids [ Time Frame: Up to 28 days ]
    Maximum observed concentration.

  2. Part 1 and Part 2: Cmin of itacitinib when administered in combination with corticosteroids [ Time Frame: Up to 28 days ]
    Minimum observed plasma or serum concentration over the dose interval.


Other Outcome Measures:
  1. Part 1 and Part 2: Response rate [ Time Frame: Up to 12 months ]
    Defined as the proportion of participants who demonstrate a CR or PR per NIH consensus guideline.

  2. Part 1: Time to response [ Time Frame: Up to 36 months ]
    Defined as the interval between randomization and first response.

  3. Part 1 and Part 2: Duration of response [ Time Frame: Up to 36 months ]
    Defined as the interval between first response and cGVHD progression, death, malignancy relapse, or initiation of new systemic cGVHD therapy.

  4. Part 1 and Part 2: Overall survival [ Time Frame: Up to 36 months ]
    Defined as the interval between the date of randomization and the date of death due to any cause.

  5. Part 1 and Part 2: Nonrelapse mortality [ Time Frame: Up to 36 months ]
    Defined as the proportion of participants who died due to causes other than malignancy relapse.

  6. Part 2: Number of treatment-emergent adverse events [ Time Frame: Up to 36 months ]
    Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Active, clinically diagnosed, moderate or severe cGVHD per NIH Consensus Criteria
  • Underwent allogeneic stem cell transplantation (allo-HCT) from any donor human leukocyte antigen (HLA) type (matched-related, matched-unrelated, or mismatched related or unrelated donor) using any graft source (bone marrow, peripheral blood stem cells, or cord blood). Recipients of myeloablative or reduced intensity conditioning are eligible.
  • Karnofsky Performance Status score ≥ 60%.
  • Evidence of myeloid and platelet engraftment (ie, absolute neutrophil count ≥ 1.0 × 10^9/L and platelet count ≥ 25 × 10^9/L).
  • Willingness to avoid pregnancy or fathering children based on protocol-defined criteria.

Exclusion Criteria:

  • Has received more than 3 days/72 hours of systemic corticosteroid treatment for cGVHD.
  • Has received any other systemic treatment for cGVHD, including extracorporeal photopheresis (ECP). Prior and concomitant use of calcineurin inhibitors as well as topical/inhaled steroids is acceptable.
  • Prior treatment with a Janus kinase (JAK) inhibitor for acute GVHD, unless the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks before randomization.
  • cGVHD occurring after a nonscheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
  • Evidence of relapsed primary malignancy or receipt of treatment for relapse after the allo-HCT was performed.
  • Corticosteroid therapy at doses > 0.25 mg/kg per day methylprednisolone or equivalent within 7 days of randomization.

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): NCT03584516


Contacts
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Contact: Incyte Corporation Call Center (US) 1.855.463.3463 medinfo@incyte.com
Contact: Incyte Corporation Call Center (ex-US) +800 00027423 globalmedinfo@incyte.com

Locations
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United States, Illinois
(USO) Illinois Cancer Specialists Recruiting
Niles, Illinois, United States, 60714
Contact    847-827-9060    leonard.klein@usoncology.com   
Principal Investigator: Dr. Leonard Klein         
United States, Ohio
(USO) - Oncology Hematology Care - Christ Hospital Recruiting
Cincinnati, Ohio, United States, 45236
Contact    513-751-2273    james.essell@usoncology.com   
Principal Investigator: Dr. James Essell         
United States, Tennessee
TriStart BMT Recruiting
Nashville, Tennessee, United States, 37203
Contact    615-342-7440    Carlos.Bachier@hcahealthcare.com   
Principal Investigator: Dr. Carlos Bachier         
United States, Texas
St. David's South Austin Medical Center Recruiting
Austin, Texas, United States, 78704
Contact    512-816-8611    Aravind.Ramakrishnan@hcahealthcare.com   
Principal Investigator: Dr. Aravind Ramakrishnan         
(USO) -Texas Oncology-Baylor Charles A. Sammons Cancer Center Blood and Marrow Transplant Recruiting
Dallas, Texas, United States, 75246
Contact    214-370-1000    jana.reynolds@usoncology.com   
Principal Investigator: Dr. Jana Reynolds         
(USO) -Texas Oncology - Medical City Dallas Building D Recruiting
Dallas, Texas, United States, 78230
Contact    972-566-4291    vikas.bhushan@usoncology.com   
Principal Investigator: Dr. Vikas Bhushan         
Sponsors and Collaborators
Incyte Corporation
Investigators
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Study Director: Rodica Morariu-Zamfir, MD Incyte Corporation

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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03584516     History of Changes
Other Study ID Numbers: INCB 39110-309
First Posted: July 12, 2018    Key Record Dates
Last Update Posted: April 24, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Incyte Corporation:
Graft-versus-host-disease
itacitinib
Janus kinase inhibitor
corticosteroids

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