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Study of Baricitinib, a JAK1/2 Inhibitor, in Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

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ClinicalTrials.gov Identifier: NCT02759731
Recruitment Status : Recruiting
First Posted : May 3, 2016
Last Update Posted : April 22, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Chronic graft versus host disease (cGVHD) can affect people who had a hematopoietic stem cell transplant using donor cells. It is often fatal. It is usually treated with high doses of steroids. But that helps only about half the people in the long term. Researchers want to see if a drug called baricitinib can help people with cGVHD that has not responded to therapy. The drug inhibits the proteins involved in communication in the immune system. These proteins may play a role in cGVHD and other inflammatory diseases.

Objectives:

To test the safety and effectiveness of baricitinib in people with cGVHD that has not responded to therapy.

Eligibility:

Adults 18 and older with cGVHD that has not responded to therapy.

Design:

Participants will be screened with a medical history, physical exam, and blood and urine tests. They will have lung and heart tests and chest scans.

Baseline visit: Participants will have:

Medical history

Physical exam

Blood tests

Tests for infectious diseases

Skin, eye, and teeth evaluations

Rehabilitation and occupational medicine evaluations

Photos of any lesions

Gynecology evaluation (females)

The study will occur in 28-day cycles. Participants will take the study drug by mouth every day for 3 cycles. Some will take it for 3 or 6 more cycles.

Participants will have a few visits during each cycle. They will repeat some previous tests. They may also have scans and questionnaires.

Participants will have a visit when they stop taking the drug and another 3 months later. They will repeat a few study tests. They will have follow-up calls for 2 years.


Condition or disease Intervention/treatment Phase
Chronic Graft vs Host Disease Chronic Graft-Versus-Host Disease Drug: Baricitinib Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 31 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of Baricitinib, a JAK1/2 Inhibitor, in Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (SCT)
Actual Study Start Date : November 1, 2016
Estimated Primary Completion Date : January 1, 2020
Estimated Study Completion Date : June 1, 2020


Arm Intervention/treatment
Experimental: Arm 1
Baricitinib starting at a dose of 2mg daily for 12 weeks. If the response at 12 weeks is a CR and there has not been a DLT, the dose will be remain at 2mg daily for an additional 12 weeks. If there has been a DLT within the first 4 weeks, the dose will be decreased to 1mg daily, and will continue at this dose as tolerated. If there has been DLT at this dose (1 mg), patients will be taken off treatment.
Drug: Baricitinib
Cycle=28 days: Baricitinib: 1mg-4mg PO QD

Experimental: Arm 2
If the response is a PR or stable disease (from cohort 1), the dose will be increased to 4mg daily for an additional 12 weeks. If there has been a DLT within the first 4 weeks will have a dose reduction back to 2mg daily. For patients who experience cGVHD progression at any time within the first 12 weeks on 2mg daily, the dose can be increased to 4mg daily until 24 weeks.
Drug: Baricitinib
Cycle=28 days: Baricitinib: 1mg-4mg PO QD




Primary Outcome Measures :
  1. To evaluate the safety of baricitinib [ Time Frame: every 2 weeks during the first 4 weeks of each dose level then every 4 weeks. ]
    Safety

  2. To evaluate the efficacy of baricitinib [ Time Frame: 24 weeks ]
    Efficacy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

-INCLUSION CRITERIA:

  1. Moderate or severe cGVHD (after allogeneic hematopoietic stem cell transplantation) diagnosed and staged per NIH criteria. Responses to JAK inhibitors have not been restricted to specific organs, so any organ involvement is eligible.
  2. Age greater than or equal to 18 years of age. Because inadequate dosing or adverse event data are currently available on the use of baricitinib in patients <18 years of age, children are excluded from this study.
  3. Karnofsky performance score >50%
  4. Chronic GVHD that did not respond to high-dose corticosteroids (prednisone at 1.0 mg/kg/day for at least 1 week or prednisone at 0.5 mg/kg/day or 1 mg/kg every other day for at least 4 weeks), or second-line therapy (any).
  5. If patient is taking systemic therapy for cGVHD at the time of enrollment, they must be on a stable or tapering doses in the preceding 4 weeks.
  6. Patients must have normal organ and marrow function as defined below:

    absolute neutrophil count greater than or equal to 1,000/mcL

    absolute lymphocyte count greater than or equal to 500/mcL

    platelets greater than or equal to 50,000/mcL

    hemoglobin greater than or equal to 9 g/dL

    total bilirubin less than or equal to 1.5 X institutional upper limit of normal, unless there is a known history of Gilbert s disease

    AST(SGOT)/ALT(SGPT) less than or equal to 3 X institutional upper limit of normal

    • Creatinine < 1.5 times the upper limit of normal, or:

    creatinine clearance greater than or equal to 50 mL/min/1.73 m^2. Creatinine clearance should be calculated per institutional standard.

  7. Primary malignancy for which the patient received transplant has been stable for 3 months prior to enrollment on study.
  8. The effects of baricitinib on human fetal development are unknown. Women of child-bearing potential and men must agree to use 2 effective forms of contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and for at least 7 days after study drug exposure. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, or if a man s partner becomes pregnant or suspects she is pregnant while he is participating in this study, she or he should inform their treating physician immediately.
  9. Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

  1. Systemic immune suppression or systemic therapy for cGVHD started within preceding 4 weeks.
  2. Hypersensitivity to JAK inhibitors.
  3. Any serious medical condition within the previous 4 weeks which places the subject at an unacceptable risk if he or she were to participate in the study or confounds the ability to interpret data from the study, including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmias, acute kidney injury, or psychiatric illness/social situations that would limit compliance with study requirements.
  4. Uncontrolled infection, including active HIV-1, Hepatitis B (HBV) and/or Hepatitis C (HCV) infection (positive HBV or HCV viral load in the setting of positive HBV core antibody or surface antibody or HCV antibody). History of HBV or HCV is allowed if there is no uncontrolled viral infection. Because the study agent may impact response to infections, patients with any active viral infection are excluded.
  5. Recurrent or progressive malignancy requiring anticancer treatment.
  6. Other cancer except that for which the transplant was done <2 years before study entry, except non-melanoma skin cancer or carcinoma in situ of the uterine cervix or breast.
  7. Patients who are receiving any other investigational agents.
  8. NIH lung score 3.
  9. Pregnant women are excluded from this study because the teratogenic effects of baricitinib are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with baricitinib, breastfeeding should be discontinued if the mother is treated with this agent.

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): NCT02759731


Contacts
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Contact: Steven Z Pavletic, M.D. (240) 760-6174 sp326h@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Steven Z Pavletic, M.D. National Cancer Institute (NCI)

Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02759731     History of Changes
Other Study ID Numbers: 160094
16-C-0094
First Posted: May 3, 2016    Key Record Dates
Last Update Posted: April 22, 2019
Last Verified: February 4, 2019

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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 National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Murine Models
Rheumatoid Arthritis
Corticosteroids
Systemic Therapy
Inflammatory Cytokines

Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases