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Chronic Graft-versus-host-diseasePhase 2NCT04200365

A Study of Itacitinib for the Treatment of Chronic Graft Versus Host Disease (cGVHD)

A Phase 2 study testing Itacitinib in people with Chronic Graft-versus-host-disease, run by SCRI Development Innovations, LLC at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study is being done in patients who have been receiving corticosteroids or other immunosuppressive therapies for the treatment of cGVHD for at least 6 months. The purpose of this study is to find out if itacitinib in combination with corticosteroids or other immunosuppressive therapies is safe and effective in… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Graft-versus-host-disease
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
15 participants
Where
5 sitesUnited States
Study dates
5 Jun 2020to 7 Sep 2023
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent signed by the patient or legal guardian prior to any study-related screening procedures
  • Patients who have undergone allo-hematopoietic stem cell transplant(s) (HSCT) from any donor HLA type (related or unrelated donor with any degree of HLA matching) using any graft source (bone marrow, peripheral blood stem cells, or cord blood). Recipients of non-myeloablative, myeloablative, and reduced intensity conditions are eligible.
  • Active, clinically diagnosed, moderate or severe cGVHD per NIH Consensus Criteria:
  • Moderate cGVHD: at least 1 organ (except lung) with a score of 2, ≥3 organs involved with a score of 1 in each organ, or lung score of 1
  • Severe cGVHD: at least 1 organ with a score of 3, or lung score of 2 or 3
  • cGVHD must be refractory to steroids defined by at least one criteria:
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  • Patient is refractory to glucocorticoid therapy at screening: ongoing treatment with prednisone equivalent ≥0.20 mg/kg/day x 4 weeks (wks) at screening and organ progression documented 4 wks after the initiation of this regimen
  • Patient is dependent on glucocorticoid therapy at screening: treatment with a prednisone equivalent mean dose ≥0.20 mg/kg/day received for 12 wks at screening
  • Patient is intolerant to glucocorticoids at screening: ongoing treatment with prednisone equivalent ≥0.20 mg/kg/day x 4 wks at screening and presence of at least one documented glucocorticoid toxicity
  • Evidence of myeloid and platelet engraftment (absolute neutrophil count ˃1,000/mm^3 and platelet count ˃25,000/mm^3). Use of growth factors or platelet transfusions is not allowed within 7 days before screening of laboratory assessment.
  • Patients must currently be receiving systemic or other immunosuppressive therapies for the treatment of cGVHD for a duration of ˃6 months prior to start of study treatment
  • Patients must be able to swallow and retain oral medication
  • Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
  • Adequate hematologic function
  • Adequate renal function: creatinine clearance ≥30 mL/min measured or calculated by Cockcroft Gault equation
  • Patients willing to avoid pregnancy or father children based on 1 of the following:
  • Women of non-childbearing potential (i.e., surgically sterile by hysterectomy and/or bilateral oophorectomy OR ≥12 months of amenorrhea)
  • Women of childbearing potential who have a negative serum pregnancy test at screening and who agree to take appropriate precautions to avoid pregnancy from screening through safety follow-up.
  • Men who agree to take appropriate precautions to avoid fathering children from screening through safety follow-up. Male patients must also refrain from donating sperm during their participation in the study and for at least 3 months after completing the study.
  • Ability to understand the nature of this study and to comply with study and follow-up procedures

Who cannot join

  • Receiving concomitant JAK inhibitor for cGVHD; prior treatment with a JAK inhibitor for acute GVHD is permitted if treatment was stopped more than 60 days prior to study start. Patients are eligible if JAK inhibitors for treatment of cGVHD are stopped due to side effects and not due to refractoriness.
  • Treatment with any other investigational agent, device, or procedure, within 28 days (or 5 half-lives, whichever is longer) of enrollment. For previous study drugs where 5 half-lives is ≤28 days, a minimum of 10 days between termination of that study drug and administration of itacitinib is required.
  • Presence of current secondary malignancies with the exception of previously treated in situ carcinoma, cervical carcinoma Stage 1B or less, and noninvasive basal cell or squamous cell skin carcinoma.
  • Pregnant or nursing (lactating) women
  • Patients with relapsed primary malignancy, or who have been treated for relapse after the allo-HSCT was performed
  • History of progressive multifocal leukoencephalopathy
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  • Evidence of the following infections:
  • Active uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of infection progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
  • Known HIV infection
  • Active tuberculosis infection that developed after allo-HSCT
  • Active viral infection confirmed by polymerase chain reaction for the BK virus ( a polyoma virus), cytomegalovirus, Epstein-Barr virus, and human herpes virus 6
  • Active hepatitis B virus (HBV) or hepatitis C virus that requires treatment, or at risk for HBV reactivation (i.e., positive HBsAg)
  • Severe organ dysfunction unrelated to underlying GVHD including:
  • Cholestatic disorders or unresolved veno-occlusive disease of the liver (persistent bilirubin abnormalities not attributable to GVHD and ongoing organ dysfunction)
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral itacitinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowl resection)
  • Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months of enrollment, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that requires therapy
  • Significant respiratory disease that requires mechanical ventilation support or a resting O2 saturation ˂90 percent by pulse oximetry or FEV1 ˂30 percent
  • Patients requiring platelet transfusions to maintain a platelet count ˃25,000/mm^3
  • Any corticosteroid therapy for indications other than cGVHD at doses ˃1 mg/kg/day methylprednisone or equivalent within 7 days of study start
  • Patients receiving treatment with medications that interfere with coagulation or platelet function including, but not limited to, aspirin dose exceeding 81 mg/day and related drugs such as heparin or warfarin sodium. Use of low molecular weight heparin is allowed.
  • Known allergies, hypersensitivity, or intolerance to itacitinib or any of its excipients
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • South Austin Medical Center

    Austin, Texas, 78704

  • Texas Oncology - Sammons Cancer Center

    Dallas, Texas, 75246

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

  • The Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Texas Transplant Institute

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: A Pilot Study of INCB039110 (Itacitinib) for the Treatment of Steroid Refractory Chronic Graft-Versus-Host Disease

This study is being done in patients who have been receiving corticosteroids or other immunosuppressive therapies for the treatment of cGVHD for at least 6 months. The purpose of this study is to find out if itacitinib in combination with corticosteroids or other immunosuppressive therapies is safe and effective in people with cGVHD.

Read the detailed description

Graft versus host disease remains a major hurdle to improve allogeneic hematopoietic stem cell transplantation outcome, with cGVHD being associated with decreased quality of life. Suppression of the immune system with corticosteroids forms the basis of first-line therapy for management of GVHD, but sustained responses are usually seen in less than 50 percent of patients and there is no standard second- or third-line treatment for steroid refractory cGVHD. Identification of novel therapeutic targets are needed to improve outcomes. Therapeutic potential has been shown by a JAK inhibitor in the treatment of steroid refractory GVHD. Itacitinib is a novel, selective inhibitor of the JAK family of protein tyrosine kinases and will be studied here in patients with steroid refractory cGVHD.

Being tested
Itacitinib
Keywords
Chronic Graft-versus-host-disease, Allogeneic hematopoietic stem cell transplant, Corticosteroids, Immunosuppressive therapies
Medical subject headings
Bronchiolitis Obliterans Syndrome

What participants receive

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

  • ItacitinibDrug

    Also called INCB039110 adipate

    Itacitinib will be administered orally once daily for up to 24 months.

Study groups in NCT04200365
Study groupRoleWhat they receive
ItacitinibExperimentalNot described
Receives: Drug: Itacitinib

What is being measured

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

  1. cGVHD Overall Response Rate (ORR) at 6 Months on Treatment

    Defined as the rate of participants with a cGVHD response of complete response (CR) or partial response (PR) after 6 months of treatment with Itacitinib as defined by 2014 National Institutes of Health Consensus Development Project on Clinical Trials in cGVHD. CR is defined as resolution of all manifestations of cGVHD in each organ or site. PR is defined as the improvement in at least one organ or site without progression in any other organ or site.

    Measured: Response assessed Day 1 of every cycle up until the end of treatment, up to 24 months. This outcome measure is the ORR for all patients once they have been on treatment for 6 months.

Secondary outcomes (6)

  1. Number of Participants That Can Withdraw or Decrease Steroids

    Ability to withdraw or decrease steroids to ˂0.5 mg/kg of methylprednisolone or equivalent

    Measured: From first dose of itacitinib until end of study treatment, up to 24 months

  2. Overall Survival

    Overall Survival (OS) is defined as the time from the first day of study drug administration (Day 1) to death on study. Patients who are alive will be censored at the date of last known date alive.

    Measured: Every 3 months for 1 year after last dose of study treatment, up to 29 months.

  3. Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability of Itacitinib

    Adverse events will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 5.0)

    Measured: Safety will be assessed from the time that informed consent is signed until 30 days after the last dose of study treatment, up to 25 months.

  4. Number of Participants With Improvement in Quality of Life Per the Lee Symptom Scale

    Changes in symptom burden will be measured using the Lee Symptom Scale. Subscale scores and the summary score range from 0 to 100, with a higher score indicating worse symptoms.

    Measured: Quality of life will be assessed prior during screening and end of treatment, up to 24 months of treatment. Participants showing improvement in LSS score from Screening to End of Treatment are shown here.

  5. Number of Participants With Recurrence or Progression of cGVHD

    Participants will be assessed for severity of cGVHD using the Clinician-Reported Global cGVHD Activity Assessment Form and Patient-reported cGVHD Activity Assessment Form. Progression in at least one organ or site without a response in any other organ or site per NIH 2014 Consensus Development Project on Clinical Trials in cGVHD.

    Measured: cGVHD status will be assessed at cycle 1 day 1, day 1 of every cycle and at the end of treatment, up to 24 months

  6. Relapse Rate of Underlying Malignancy

    Participants will be closely monitored for any evidence of underlying disease relapse or recurrence. Formal re-staging will be done at physician discretion.

    Measured: Relapse of underlying malignancy will be assessed on Day 1 of each cycle, at end of treatment and survival follow-up. Follow-up visits every 3 months for 1 year after last dose of study treatment, up to 29 months

Timeline

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

  1. First posted16 Dec 2019
  2. Study start5 Jun 2020
  3. Primary completion7 Sep 2023
  4. Study completion7 Sep 2023

Why it stopped: Slow enrollment and PI departure

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
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04200365
Sponsor's protocol ID
BMT29
Status last verified
Aug 2024
First submitted
10 Dec 2019
Last updated
6 Nov 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Itacitinib in people with Chronic Graft-versus-host-disease, run by SCRI Development Innovations, LLC at 5 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 20 inclusion and 22 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: stopped early, as of the sponsor's last update on 6 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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 Nov 2024). 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?

cGVHD Overall Response Rate (ORR) at 6 Months on Treatment (time frame: Response assessed Day 1 of every cycle up until the end of treatment, up to 24 months. This outcome measure is the ORR for all patients once they have been on treatment for 6 months.). 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 NCT04200365.

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 Nov 2024.

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