Ibrutinib Plus Rituximab for cGVHD Following Allo-SCT
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|ClinicalTrials.gov Identifier: NCT03689894|
Recruitment Status : Recruiting
First Posted : October 1, 2018
Last Update Posted : August 13, 2019
Allogeneic stem cell transplant is used to treat a variety of blood cancers. However, graft-versus-host disease (GVHD) is a common condition that may occur after transplant. GVHD happens when the donor cells attack and damage the recipients' tissue.
The standard medication to treat chronic graft-versus-host-disease (cGVHD) is corticosteroids. However, there are long-term side effects of steroid therapy, including risk of infection, bone loss and other health problems. In addition, some patients with cGVHD do not respond to standard steroid therapy. In these cases, medications to suppress the immune system may be used.
The purpose of this study is to learn about the effects, both good and bad, of combining the drugs ibrutinib and rituximab for the treatment of cGVHD.
Ibrutinib is Food and Drug Administration (FDA)-approved for the treatment of cGVHD which has not responded to steroid therapy.
Rituximab is an investigational drug, which means it is not FDA approved for this particular use. Rituximab is currently approved for treatment of Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), and other conditions, but is not FDA approved for the treatment of cGVHD.
However, rituximab has been used in a clinic setting for the treatment of cGVHD in a number of patients over the past few years, and has generally been well tolerated and shown some benefit.
The combination of ibrutinib and rituximab is being studied in the treatment of certain types of lymphoma and chronic leukemia, but it has not yet been combined for patients with cGVHD. Because ibrutinib is not approved for this use when combined with rituximab, it is considered investigational in this study.
In this form, the term "study drug" refers to ibrutinib and rituximab.
This study will involve people who have chronic GVHD, have previously taken corticosteroids, and have either not benefited from treatment with corticosteroids or have been unable to successfully taper off steroids.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Graft-versus-host-disease||Drug: Ibrutinib Drug: Rituximab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Combination Ibrutinib and Rituximab for the Treatment of Chronic Graft-Versus-Host Disease Following Allogeneic Stem Cell Transplant|
|Actual Study Start Date :||April 12, 2019|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2024|
Experimental: Ibrutinib plus Rituximab
*375 milligrams (mg) per meter squared intravenous infusion weekly for 4 (may repeat 8 weeks after initial therapy, if suboptimal response)
Subjects will receive oral (PO) Ibrutinib 140 mg once daily with Rituximab 375 mg per meter squared IV weekly x4 (with pre-medications and infusion procedure as per standard protocol) Rituximab Pre-medications:Acetaminophen 650 mg PO; Diphenhydramine 25 mg PO/IV; Dexamethasone 20 mg IV.
If no adverse events >Grade 3+ are noted after 1 week, the Ibrutinib dose schedule will be increased to 280 mg daily. If no adverse events >Gr3+ are noted after an additional 1 week, the Ibrutinib dose will be increased to 420 mg daily.
Subject will receive an intravenous infusion of 375mg per meter squared weekly for 4 weeks, which may be repeated 8 weeks after initial therapy if only a suboptimal response is achieved.
- Evaluate dose-limiting toxicities experienced in subjects treated with Ibrutinib plus Rituximab [ Time Frame: Start of treatment through Week 4 of treatment ]During dose escalation, subjects will be assessed for dose-limiting toxicities at each dose level.
- Assess the response rate of cGVHD to treatment with Ibrutinib plus Rituximab [ Time Frame: 6 weeks, 3 months, and 6 months after initiation of treatment ]Response rate of clinically significant GVHD will be assessed using NIH criteria (from 2014 NIH Consensus Development Project).
- Identify relevant laboratory correlates underlying clinical response, or lack thereof. [ Time Frame: 6 weeks, 3 months, and 6 months after initiation of treatment ]Plasma ST2 and CD4CD25FOXp3 correlates will be measured at identified intervals to determine if either correlate demonstrates an affect on clinical response.
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): NCT03689894
|Contact: Research Nurse||(800) firstname.lastname@example.org|
|Principal Investigator:||John M Hill, MD||Dartmouth-Hitchcock Medical Center|