Study Results
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View full resultsBasic Information
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TERMINATED
PHASE1/PHASE2
2 participants
INTERVENTIONAL
2019-04-11
2021-09-20
Brief Summary
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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.
Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Ibrutinib plus Rituximab
Rituximab
\*375 milligrams (mg) per meter squared intravenous infusion weekly for 4 (may repeat 8 weeks after initial therapy, if suboptimal response)
Ibrutinib
* 420 mg (140 mg capsule x3) by mouth daily
* May be given beyond 3-6 months (for maintenance).
Ibrutinib
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.
Rituximab
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.
Interventions
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Ibrutinib
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.
Rituximab
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.
Eligibility Criteria
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Inclusion Criteria
2. Chronic GVHD that is confirmed by clinical assessment and/or biopsy.
3. Either steroid-refractory or steroid-dependent cGVHD.
4. Karnofsky performance status ≥ 60.
Exclusion Criteria
2. Renal insufficiency as follows: creatinine \> 2.5 mg/deciliters (dL) or Creatinine Clearance \< 30 ml/min.
3. Hepatic insufficiency as follows: serum bilirubin \>3 mg/dL or transaminitis \>3x upper limit of normal (ULN) (unless deemed due to GVHD).
4. History of cardiac dysrhythmias or known cardiovascular disease without formal Cardiology clearance.
5. History of cerebro-vascular accident or intracranial hemorrhage within 6 months prior to enrollment.
6. History of non-intracranial hemorrhage and/or coagulopathy without formal Coagulation clearance.
7. Uncontrolled infections not responsive to antibiotics, anti-viral medicines, or anti-fungal medicines; or infection requiring systemic treatment that was completed ≤14 days before enrollment.
8. History of other hematologic malignancy.
9. History of human immunodeficiency virus (HIV).
10. History of active hepatitis B virus (HBV) or hepatitis C virus (HCV) without formal Infectious Disease clearance.
11. Patients incapable of complying with routine follow up schedule or unable to be compliant with study therapy.
12. Active or within 3 months use of prohibited medications or substances (e.g., illicit drugs).
18 Years
ALL
No
Sponsors
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Dartmouth-Hitchcock Medical Center
OTHER
Responsible Party
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John M. Hill, Jr., MD
Directory, Allogeneic Transplant Program
Principal Investigators
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John M Hill, MD
Role: PRINCIPAL_INVESTIGATOR
Dartmouth-Hitchcock Medical Center
Locations
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Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States
Countries
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References
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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D17120
Identifier Type: -
Identifier Source: org_study_id