Ibrutinib (PCI-32765) in Waldenstrom's Macroglobulinemia

January 10, 2020 updated by: Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

63

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94305
        • Stanford University
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02215
        • Brigham and Women's Hospital
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment Arm
PCI-32765; ibrutinib
Drug: PCI-32765
Taken orally, once daily in the morning
Other Names:
  • ibrutinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: 4 years
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
Time Frame: 4 years
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
Time Frame: 6 years
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 Frame: 6 years
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
Time Frame: 4 years
To assess the major response rate (>50% reduction in serum IgM from baseline)
4 years
Very Good Partial Response Rate
Time Frame: 4 years
To assess the very good partial response rate (>90% reduction in serum IgM from baseline)
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Investigators

  • Principal Investigator: Steven P Treon, MD PhD, Dana-Farber Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 1, 2012

Primary Completion (ACTUAL)

September 9, 2016

Study Completion (ACTUAL)

September 15, 2018

Study Registration Dates

First Submitted

May 17, 2012

First Submitted That Met QC Criteria

June 7, 2012

First Posted (ESTIMATE)

June 8, 2012

Study Record Updates

Last Update Posted (ACTUAL)

January 21, 2020

Last Update Submitted That Met QC Criteria

January 10, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12-015

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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