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Low Risk Acute Graft-versus-host DiseasePhase 2NCT03846479

Itacitinib for Low Risk GVHD

A Phase 2 study testing Itacitinib in people with Low Risk Acute Graft-versus-host Disease and Graft-versus-host-disease, run by John Levine at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Graft-versus-host disease (GVHD) is treated with high doses of systemic steroids which can lead to serious complications. A new blood test can identify patients whose GVHD is most likely to respond to well to treatment (low risk GVHD). Read more about this study

Who is it for?
Ages 12 to 75 years
What is being tested?
Itacitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
14 sitesUnited States
Study dates
25 Mar 2019to 11 May 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Newly diagnosed GVHD that meets criteria for Minnesota standard risk
  • Ann Arbor 1 GVHD by biomarkers
  • GVHD not previously treated systemically (topical therapies and non-absorbed steroids are allowed)
  • Any donor type, HLA-match, conditioning regimen is acceptable
  • Age 12 - 75 years (children <18 years must also weigh 50 kg or more)
  • Patients must be engrafted post-transplant (ANC >500/μL and platelet count >20,000). Use of growth factor supplementation to maintain neutrophil count is allowed.
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  • Direct bilirubin must be <2 mg/dL unless the elevation is known to be due to Gilbert syndrome within 3 days prior to enrollment.
  • ALT/SGPT and AST/SGOT must be <5x the upper limit of the normal range within 3 days prior to enrollment.
  • Signed and dated written informed consent obtained from patient or legal representative.

Who cannot join

  • Patients currently being treated with any JAK inhibitor including ruxolitinib
  • Relapsed, progressing, or persistent malignancy requiring withdrawal of systemic immune suppression
  • Patients with uncontrolled infection (i.e., progressive symptoms related to infection despite treatment or persistently positive microbiological cultures despite treatment or any other evidence of severe sepsis)
  • Severe organ dysfunction including requirement for dialysis, mechanical ventilation or oxygen supplementation exceeding 40% FiO2 within 7 days of enrollment.
  • Creatinine clearance or estimated glomerular filtration rate <30 ml/min as calculated by institutional practice (e.g., Cockcroft-Gault equation, CKD-EPI equation, etc)
  • A clinical presentation resembling de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment
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  • Patients receiving corticosteroids >10 mg/day prednisone (or other steroid equivalent) for any indication within 7 days before the onset of acute GVHD except for adrenal insufficiency or premedication for transfusions/IV meds
  • Patients who are pregnant
  • Patients receiving investigational agents within 30 days of enrollment. However, the Principal Investigator (PI) may approve prior use of an investigational agent if the agent is not expected to interfere with the safety or the efficacy of itacitinib
  • History of allergic reaction to itacitinib or any JAK inhibitor

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Emory University

    Atlanta, Georgia, 30003

  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30322

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Ohio State University

    Columbus, Ohio, 43210

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • University of Kansas Cancer Center

    Fairway, Kansas, 66205

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Children's Hospital of Los Angeles

    Los Angeles, California, 90027

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • The Mount Sinai Hospital

    New York, New York, 10029

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • University of Pennsylvania, Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Itacitinib Monotherapy for Low Risk Graft-vs-Host Disease

Graft-versus-host disease (GVHD) is treated with high doses of systemic steroids which can lead to serious complications. A new blood test can identify patients whose GVHD is most likely to respond to well to treatment (low risk GVHD). This study will test whether patients with low risk GVHD can be successfully treated without steroids. Patients who participate with this study will be treated with itacitinib instead of steroids. Itacitinib is an experimental drug with an excellent safety record and appears to have activity as a GVHD treatment.

Read the detailed description

Patients with newly diagnosed low risk acute GVHD defined as Minnesota standard risk based on symptoms and Ann Arbor 1 GVHD based on biomarkers were eligible if they met all other eligible criteria (see eligibility criteria below). Enrolled patients were required to start treatment within 4 days of confirmation of Ann Arbor 1 status. Treatment consisted of itacitinib 200 mg daily for 28 days. Patients with a clinical response on day 28 were eligible for a second 28 day cycle of itacitinib 200 mg daily. Missed doses could be made up by extending the treatment duration for up to 2 additional weeks. Medications given for GVHD prophylaxis and topical treatments for GVHD were allowed. Supportive care was provided according to institutional standards. Itacitinib was permanently discontinued after any of the following:

administration of 56 doses of itacitinib or initiation of systemic corticosteroids or any other systemic treatment for GVHD or patient withdrawal from the study or general or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator OR ten weeks elapsed since the first dose of itacitinib.

Being tested
Itacitinib
Keywords
Graft-versus-host disease, Itacitinib
Medical subject headings
Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ItacitinibDrug

    Also called INCB389110

    for up to 56 days

Study groups in NCT03846479
Study groupRoleWhat they receive
ItacitinibExperimentalItacitinib 200 mg administered orally daily
Receives: Drug: Itacitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients Who Achieve CR or PR by Day 28 of Treatment

    Number of patients who achieve CR or PR by day 28 of treatment with itacitinib without the addition of any other systemic GVHD treatment including steroids.

    Complete Response (CR): All evaluable organs (skin, liver, GI tract) stage 0. For a response to be scored as CR on day 28, the patient must be in CR on that day and have had no intervening additional GVHD therapy.

    Partial Response (PR): An improvement in one or more organ involved with GVHD symptoms without worsening in others. For a response to be scored as PR on day 28, the patient must be in PR on that day and have had no intervening additional GVHD therapy.

    Measured: Day 28

  2. Number of Participants Who Developed Steroid Refractory GVHD

    Number of participants who developed steroid refractory GVHD within 28 days of starting steroids. Steroid-refractory GVHD (defined as GVHD that worsens (increase by one or more grade) after 3 days, or fails to respond to treatment within 7 days (for GVHD grade III) or 14 days (for GVHD grade II) or 2nd line therapy beyond systemic steroid treatment is begun within 28 days of starting steroids.

    Measured: Day 28

Secondary outcomes (6)

  1. Number of Participants With Serious Infectious

    Number of participants who developed serious infections by day 90. Serious infectious complications is defined as any viral and bacterial infections requiring treatment and proven fungal infections.

    Measured: Day 90

  2. Number of Participants Alive at 6 Months and 1 Year

    Number of overall survival (OS), defined as the duration from the date of diagnosis to death or last follow-up, with no restriction on the cause of death.

    Measured: 6 months and 1 year

  3. Number of Participants With Non-relapse Mortality (NRM)

    Number of participants with non-relapse mortality (NRM) at 6 months and 1 year

    Measured: 6 months and 1 year

  4. Number of Participants Who Relapsed

    Number of participants who relapsed by 6 months and by 1 year

    Measured: 6 months and 1 year

  5. Number of Participants Who Developed Chronic GVHD

    Number of participants who developed chronic GVHD requiring systemic treatment at 1 year

    Measured: 1 year

  6. Cumulative Steroid Dose

    Cumulative steroid dose (over 4 weeks) in patients who receive steroids as second line therapy

    Measured: Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2019
  2. Study start25 Mar 2019
  3. Primary completion7 May 2021
  4. Study completion11 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Open label, single arm, non-inferiority study
Masking
None (open label)
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03846479
Sponsor's protocol ID
GCO 18-1684
Status last verified
Feb 2023
First submitted
17 Feb 2019
Last updated
6 Feb 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Etra A, Capellini A, Alousi A, Al Malki MM, Choe H, DeFilipp Z, Hogan WJ, Kitko CL, Ayuk F, Baez J, Gandhi I, Kasikis S, Gleich S, Hexner E, Hoepting M, Kapoor U, Kowalyk S, Kwon D, Langston A, Mielcarek M, Morales G, Ozbek U, Qayed M, Reshef R, Rosler W, Spyrou N, Young R, Chen YB, Ferrara JLM, Levine JE. Effective treatment of low-risk acute GVHD with itacitinib monotherapy. Blood. 2023 Feb 2;141(5):481-489. doi: 10.1182/blood.2022017442.

    PubMed 36095841

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Itacitinib in people with Low Risk Acute Graft-versus-host Disease and Graft-versus-host-disease, run by John Levine at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients Who Achieve CR or PR by Day 28 of Treatment (time frame: Day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03846479, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2023.

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