Ibrutinib (PCI-32765) in Waldenstrom's Macroglobulinemia

Study Overview
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Brief Summary
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This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug, PCI-32765, to learn whether PCI-32765 works in treating a specific cancer. Investigational means that PCI-32765 is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if PCI-32765 is effective for treating different types of cancer. It also means that the FDA has not yet approved PCI-32765 for use in patients, including people with Waldenstrom's Macroglobulinemia. PCI-32765 is a newly discovered drug that is being developed as an anti-cancer agent. PCI-32765 is a Bruton's tyrosine kinase (Btk) inhibitor drug which interrupts B cell receptor (BCR) signaling in lymphomas by selectively and irreversibly binding to the Btk protein, which then results in malignant cell death. This drug has been used in laboratory experiments and other research studies in B-cell malignancies and information from those other research studies suggests that PCI-32765 may be a treatment strategy for B-cell malignancies, including Waldenstrom's Macroglobulinemia. In this research study, the investigators are testing the safety and efficacy of PCI-32765 as a treatment option for relapsed or refractory Waldenstrom's Macroglobulinemia.

Detailed Description
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Patients in this research study will receive up to 40 cycles of treatment. Each treatment cycle lasts 4 weeks. Patients will take PCI-32765 by mouth, once a day in the morning. During each cycle patients will be asked to visit the clinic for scheduled tests and exams and to receive a supply of PCI-32765 to take at home every day. Patients will visit the clinic on the first day of each of the first 3 cycles, and then just once at the beginning of every three cycles. During study visits, patients will have a physical exam where they will be asked questions about their general health and specific questions about any problems that they might be having and any medications they may be taking. Patients will have blood tests to see how their disease is responding to the study treatment and how they are tolerating the study drug. Patients may also have CT scans of the chest, abdomen and pelvis as well as a bone marrow aspirate and biopsy. If a patient's disease stays the same or is helped, he/she will continue to get study treatment. If disease worsens, he/she will be taken off study treatment at that time. After completion of the treatment and as part of standard of care, follow-up tests will include a physical exam, review of symptoms and medications, blood tests, bone marrow aspirate and biopsy, CT scans of the chest, abdomen and pelvis. The investigators would like to continue to monitor progress by following-up every three months for up to two years after completion of study treatment or until next treatment, whichever comes first.

Official Title
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Phase 2 Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, Ibrutinib (PCI-32765), in Waldenstrom's Macroglobulinemia

Conditions
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Waldenstrom's Macroglobulinemia

Intervention / Treatment
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* Drug: PCI-32765


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinicopathological diagnosis of Waldenstrom's Macroglobulinemia Measurable disease Have received at least one prior therapy for WM therapies Disease free of prior malignancies Able to adhere to study visit schedule and other protocol requirement Exclusion Criteria: Pregnant or breastfeeding Any other serious medical condition Concurrent use of other anti-cancer agents or treatments Prior exposure to PCI-32765 Known CNS lymphoma Significant cardiovascular disease Any disease affecting gastrointestinal function

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>PCI-32765; ibrutinib | Drug: PCI-32765<br>* Taken orally, once daily in the morning<br>* Other names: ibrutinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | To assess the overall response rate (>25% reduction in serum IgM from baseline). | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of PCI-32765 | To assess the safety and tolerability of PCI-32765 in symptomatic WM patients with relapsed/refractory disease. Grade > or = 2 Adverse Events determined to be associated with PCI-32765 and subsequent outcomes will constitute the safety profile of PCI-32765 in WM. Percent of participants who experienced at least 1 grade 2 or higher treatment emergent adverse event. | 4 years | 
| Determine Progression Free Survival | To determine Progression Free Survival (PFS in symptomatic WM patients with relapsed/refractory disease. Participants were treated for 40 cycles and then followed for 2 years or until next therapy or death. 40 participants were censored prior to disease progression. | 6 years | 
| To Determine Time to Next Therapy (TTNT) of PCI-32765 in Symptomatic WM Patients With Relapsed/Refractory Disease | Time to Next Therapy is the duration of time from of starting ibrutinib until next therapy. Participants were treated for 40 cycles and then followed for 2 years or until next therapy or death. Participants had the option to continue ibrutinib commercially. 40 participants were censored while still on commercial ibrutinib therapy. | 6 years | 
| Major Response Rates | To assess the major response rate (>50% reduction in serum IgM from baseline) | 4 years | 
| Very Good Partial Response Rate | To assess the very good partial response rate (>90% reduction in serum IgM from baseline) | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed, Refractory