Front Line Ibrutinib for Newly Diagnosed Chronic Graft-Versus Host Disease
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|ClinicalTrials.gov Identifier: NCT04294641|
Recruitment Status : Recruiting
First Posted : March 4, 2020
Last Update Posted : October 27, 2020
Chronic Graft Versus Host Disease (cGVHD) can occur after a person has had a stem cell or bone marrow transplant. In cGVHD, the donor cells attack the recipient s body. Researchers want to see if a drug called ibruntinib can block one of the proteins that lead to the immune reaction that causes cGVHD.
To see if ibrutinib as a first-line treatment can help people with newly diagnosed cGVHD.
People age 18 and older with newly diagnosed moderate or severe cGVHD
Participants will be screened with
medical and medicine histories
physical exam and vital signs
electrocardiograms (to measure heart function)
assessment of their ability to perform daily activities
blood and urine tests
assessment of their general well-being.
Participants will visit the Clinical Center every 2 weeks for the first 2 months. Then they will visit every 4 weeks.
Participants will take ibrutinib by mouth once every day of every cycle. One cycle is 28 days. Treatment will last up to 2 years. Participants will keep a medicine diary.
Participants will take tests to measure lung function. They may have computed tomography scans of their chest. They will complete questionnaires about their symptoms and how cGVHD is affecting their body and quality of life. They will repeat the screening tests.
Participants may have optional blood tests and/or skin biopsies to better understand the drug s effect on the body.
Participants will be contacted by phone 30 days after treatment ends. They will also be contacted once a year for 2 years to discuss how they are feeling and if they have taken any other medicines to treat cGVHD.
|Condition or disease||Intervention/treatment||Phase|
|Chronic GVHD||Drug: Ibrutinib||Phase 2|
- Chronic graft-versus-host disease (GvHD) is the leading cause of late morbidity and non-relapse mortality following allogeneic hematopoietic stem cell transplantation (alloHSCT), occurring in 40-60% long-term survivors.
- Chronic GvHD occurs due to the dysfunctional peripheral tolerance during post-transplant hematopoietic reconstitution that allows the development and persistence of alloreactive donor-derived T and B cells.
- Prednisone is the front-line therapy; however, about 50% of patients have steroid-refractory disease and there is no standard second-line therapy.
- The most attractive approach for controlling chronic GvHD would be early therapy intervention which could prevent the most severe and irreversible clinical manifestations.
- Anti-B-cell therapy delivered early in chronic GvHD could be effective and steroid-sparing.
- Ibrutinib, reversible small molecule inhibitor of Bruton s tyrosine kinase, has been shown to be well-tolerated and effective in phase 1b/2 trial for steroid refractory chronic GvHD.
-To evaluate efficacy of ibrutinib as a first-line treatment for persons with newly diagnosed chronic GvHD by measuring the overall response rate (complete response [CR] + partial response [PR]) at 6 months, according to the 2014 NIH Consensus Criteria
- Newly diagnosed, moderate or severe chronic GvHD according to the 2014 NIH Consensus Criteria, requiring systemic immunosuppression
- Age greater than or equal to 18 years old
- Karnofsky performance status greater than or equal to 60%
- History of prior alloHSCT; any donors, conditioning regimens and graft sources are allowed
- Adequate cardiac, hepatic and other organ function
- Adequate laboratory parameters
- Multi-center, non-randomized, phase II study
- Two-stage design will be used to determine the overall response rate (CR + PR) at 6 months
- Continuous daily dose of ibrutinib 420 mg by mouth, with the potential for dose reductions to 280 mg and 140 mg
- The accrual ceiling will be set at 40 patients, allowing for a total of up to 28 evaluable subjects.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Front Line Ibrutinib for Newly Diagnosed Chronic Graft-Versus-Host Disease|
|Estimated Study Start Date :||October 30, 2020|
|Estimated Primary Completion Date :||June 24, 2022|
|Estimated Study Completion Date :||June 28, 2024|
Determine response rate via continuous daily dose by mouth to determine efficacy
140 mg capsules for a dose of 420 mg daily for up to 12 months.
- To evaluate the efficacy of ibrutinib as a first-line treatment for persons with newly diagnosed chronic graft-versus-host disease(GvHD) by measuring the overall response rate [ Time Frame: 6 months ]measuring the overall response rate (complete response [CR] + partialresponse [PR]) according to the 2014 NIH Consensus Criteria.
- To evaluate safety of ibrutinib for newly diagnosed chronic GvHD [ Time Frame: 6 months ]Safety of the agent will be assessed by determining the grade of adverse events
- To evaluate failure-free survival (FFS) [ Time Frame: 6 months ]Time to event endpoints such as failure free survival will be determined using a Kaplan-Meier curve.
- To evaluate 24 months post-treatment follow-up for survival [ Time Frame: 6 months ]Survival will be determined using a Kaplan-Meier curve at 24 months.
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): NCT04294641
|Contact: Steven Z Pavletic, M.D.||(240) email@example.com|
|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|
|United States, Missouri|
|Washington University, St. Louis||Recruiting|
|Saint Louis, Missouri, United States, 63110|
|Contact: Iskra Pusic, M.D. 314-747-8465 firstname.lastname@example.org|
|Principal Investigator:||Steven Z Pavletic, M.D.||National Cancer Institute (NCI)|