Graft-versus-host-diseasePhase 1NCT04131738
Baricitinib for the Prophylaxis of Graft-Versus-Host Disease After Peripheral Blood Hematopoietic Cell Transplantation
A Phase 1 study testing Baricitinib in people with Graft-versus-host-disease and Graft Vs Host Disease, run by Washington University School of Medicine at 1 site in United States.
Trial summary
In this trial, the investigators will begin to explore the possibility that, as in mice, JAK1/2 inhibition with hematopoietic cell transplantation (HCT) may mitigate graft-versus-host-disease (GVHD) while retaining engraftment and Graft-versus-Leukemia (GVL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft-versus-host-disease, Graft Vs Host Disease
- What is being tested?
- Baricitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Apr 2020to 17 Aug 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Patients must meet the following criteria within 30 days prior to Day 0 unless otherwise noted.
- Diagnosis of a hematological malignancy listed below:
- Acute myelogenous leukemia (AML) in complete morphological remission (based on IWG Criteria).
- Acute lymphocytic leukemia (ALL) in complete morphological remission (MRD negative, based on IWG Criteria).
- Myelodysplastic syndrome with less than 10% blasts in bone marrow.
- Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete or partial remission.
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- Planned treatment is myeloablative or reduced intensity conditioning followed by peripheral blood HLA matched donor transplantation
- Available HLA-identical donor who meets the following criteria:
- At least 18 years of age.
- HLA-identical donor/recipient match by high-resolution typing per institutional standards.
- In the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting HSC.
- No active hepatitis.
- Negative for HTLV and HIV.
- Not pregnant.
- Donor selection will be in compliance with institutional standards
- Safety Lead-In Phase: For the first three patients at each dose level, related donors must consent to a second product collection should it prove necessary.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Adequate organ function as defined below:
- Total bilirubin must be within normal range at baseline.
- AST (SGOT) and ALT (SGPT) ≤ 3.0 x IULN.
- Estimated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault Formula.
- Oxygen saturation ≥ 90% on room air.
- LVEF ≥ 40%.
- FEV1 and FVC ≥ 40% predicted, DLCOc ≥ 40% predicted. If DLCO is < 40%, patients will still be considered eligible if deemed safe after a pulmonary evaluation.
- At least 18 years of age at the time of study registration
- Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
- Must be able to receive GVHD prophylaxis with tacrolimus, mini-methotrexate with or without ATG or post transplant Cy with MMF and tacrolimus as outlined in the protocol
Who cannot join
- Must not have undergone a prior allogeneic donor (related, unrelated, or cord) transplant. Prior autologous transplant is not exclusionary.
- Known HIV or active hepatitis B or C infection.
- Known latent tuberculosis infection, or at high risk for latent TB infection, or a positive t-spot tuberculosis test
- Known hypersensitivity to one or more of the study agents, including baricitinib.
- Must not have myelofibrosis or other disease known to prolong neutrophil engraftment to > 35 days after transplant.
- Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug (Day -3).
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- Pregnant and/or breastfeeding.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune disease, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements.
- Immunosuppressive doses of steroids. Subjects with steroids for adrenal insufficiency will not be excluded.
- History of unprovoked thrombosis or known thrombophilia. Provoked and/or superficial DVTs are eligible provided they are treated and resolved at the time of screening.
- Recent (less than 1 year from screening) myocardial infarction or embolic stroke
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Single-Arm, Open-Label Phase I Clinical Trial of a JAK Inhibitor, Baricitinib, for the Prophylaxis of Graft-Versus-Host Disease After Peripheral Blood Hematopoietic Cell Transplantation
In this trial, the investigators will begin to explore the possibility that, as in mice, JAK1/2 inhibition with hematopoietic cell transplantation (HCT) may mitigate graft-versus-host-disease (GVHD) while retaining engraftment and Graft-versus-Leukemia (GVL). Both preclinical and clinical data suggest that inhibition of IFNy and IL-6, directly and using downstream JAK Inhibitors, may be an effective strategy to decrease toxicities and improve disease control for patients undergoing Allogeneic HSCT. Baricitinib, as a JAK1/2 inhibitor, has shown superiority to other JAK inhibitors in preclinical GVHD models. The purpose of this phase I clinical trial is to determine the safety of baricitinib with HSCT measured by the effect on engraftment and grade III-IV acute graft-versus-host-disease (aGVHD).
- Conditions
- Graft-versus-host-disease, Graft Vs Host Disease
- Being tested
- Baricitinib
- 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.
BaricitinibDrug
Also called Olumiant
Baricitinib may be taken without regard to food. It should be taken at the same time every day.
| Study group | Role | What they receive |
|---|---|---|
| Baricitinib 2 mg Dose Level | Experimental | * On Day 0 the allograft will be infused per standard institutional practice
* Baricitinib will be administered PO at a starting dose of 2 mg daily from Day -3 to Day 100
* After Day 100, for patients already dose reduced to 2 mg daily, reduce baricitinib to 2 mg every other day for one month or 1 mg daily for one month (depending on drug supply) then discontinue. Receives: Drug: Baricitinib |
| Baricitinib 4 mg Dose Level | Experimental | * On Day 0 the allograft will be infused per standard institutional practice
* Baricitinib will be administered PO at a starting dose of 4 mg daily from Day -3 to Day 100
* After Day 100, for patients at a dose of 4 mg daily, reduce baricitinib to 2 mg daily for one month, then every other day for one month or 1 mg daily for one month (depending on drug supply) then discontinue. Receives: Drug: Baricitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidence of graft failure
-Failure to engraft will be defined as failure to achieve absolute neutrophil count > 500 for 3 days by Day 28.
Measured: 28 days post transplant
Cumulative incidence of grade III-IV acute GVHD
-Acute GVHD will be assessed using MAGIC criteria
Measured: Day 100
Secondary outcomes (1)
Treatment related mortality
-Death that results from a transplant procedure-related complication (e.g. infection, organ failure, hemorrhage, GVHD) rather than from relapse of the underlying disease or an unrelated cause.
Measured: Day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2019
- Study start7 Apr 2020
- Primary completion30 Nov 2021
- Study completion17 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft-versus-host-diseaseStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- * If all 3 patients in the safety lead-in for the 2 mg dose level achieve engraftment, 9 additional patients will be enrolled at that dose level. * If all 3 patients in the safety lead-in for the 4 mg dose level achieve engraftment, 9 additional patients will be enrolled at that dose level.
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark A Schroeder, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04131738
- Sponsor's protocol ID
- 201911012
- Status last verified
- May 2023
- First submitted
- 16 Oct 2019
- Last updated
- 10 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Arm, Open-Label Phase I Clinical Trial of a JAK Inhibitor, Baricitinib, for the Prophylaxis of Graft-Versus-Host Disease After Peripheral Blood Hematopoietic Cell Transplantation
- ClinicalTrials.gov ID
- NCT04131738
- Acronym / sponsor ID
- 201911012
- Conditions
- Graft-versus-host-disease, Graft Vs Host Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 7 Apr 2020 (actual)
- Primary completion
- 30 Nov 2021 (actual)
- Study completion
- 17 Aug 2022 (actual)
- First posted
- 18 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this trial, the investigators will begin to explore the possibility that, as in mice, JAK1/2 inhibition with hematopoietic cell transplantation (HCT) may mitigate graft-versus-host-disease (GVHD) while retaining engraftment and Graft-versus-Leukemia (GVL). Both preclinical and clinical data suggest that inhibition of IFNy and IL-6, directly and using downstream JAK Inhibitors, may be an effective strategy to decrease toxicities and improve disease control for patients undergoing Allogeneic HSCT. Baricitinib, as a JAK1/2 inhibitor, has shown superiority to other JAK inhibitors in preclinical GVHD models. The purpose of this phase I clinical trial is to determine the safety of baricitinib with HSCT measured by the effect on engraftment and grade III-IV acute graft-versus-host-disease (aGVHD).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- * If all 3 patients in the safety lead-in for the 2 mg dose level achieve engraftment, 9 additional patients will be enrolled at that dose level. * If all 3 patients in the safety lead-in for the 4 mg dose level achieve engraftment, 9 additional patients will be enrolled at that dose level.
| Arm | Type | Receives |
|---|---|---|
| Baricitinib 2 mg Dose Level | Experimental | Drug: Baricitinib* On Day 0 the allograft will be infused per standard institutional practice * Baricitinib will be administered PO at a starting dose of 2 mg daily from Day -3 to Day 100 * After Day 100, for patients already dose reduced to 2 mg daily, reduce baricitinib to 2 mg every other day for one month or 1 mg daily for one month (depending on drug supply) then discontinue. |
| Baricitinib 4 mg Dose Level | Experimental | Drug: Baricitinib* On Day 0 the allograft will be infused per standard institutional practice * Baricitinib will be administered PO at a starting dose of 4 mg daily from Day -3 to Day 100 * After Day 100, for patients at a dose of 4 mg daily, reduce baricitinib to 2 mg daily for one month, then every other day for one month or 1 mg daily for one month (depending on drug supply) then discontinue. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Patients must meet the following criteria within 30 days prior to Day 0 unless otherwise noted.
- Diagnosis of a hematological malignancy listed below:
- Planned treatment is myeloablative or reduced intensity conditioning followed by peripheral blood HLA matched donor transplantation
- Available HLA-identical donor who meets the following criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Key exclusion criteria (11 listed)
- Must not have undergone a prior allogeneic donor (related, unrelated, or cord) transplant. Prior autologous transplant is not exclusionary.
- Known HIV or active hepatitis B or C infection.
- Known latent tuberculosis infection, or at high risk for latent TB infection, or a positive t-spot tuberculosis test
- Known hypersensitivity to one or more of the study agents, including baricitinib.
- Must not have myelofibrosis or other disease known to prolong neutrophil engraftment to > 35 days after transplant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BaricitinibAlso: OlumiantBaricitinib may be taken without regard to food. It should be taken at the same time every day. | Drug | Baricitinib 2 mg Dose Level, Baricitinib 4 mg Dose Level |
Primary outcome
Cumulative incidence of graft failure
Time frame: 28 days post transplant
-Failure to engraft will be defined as failure to achieve absolute neutrophil count > 500 for 3 days by Day 28.
Cumulative incidence of grade III-IV acute GVHD
Time frame: Day 100
-Acute GVHD will be assessed using MAGIC criteria
1 secondary outcome
Treatment related mortality
Time frame: Day 180
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark A Schroeder, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Baricitinib in people with Graft-versus-host-disease and Graft Vs Host Disease, run by Washington University School of Medicine at 1 site 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 27 inclusion and 11 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 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Cumulative incidence of graft failure (time frame: 28 days post transplant). 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?
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 10 May 2023.