Clinical trial NCT01614821: Ibrutinib (PCI-32765) in Waldenstrom's Macroglobulinemia
Official title: Phase 2 Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, Ibrutinib (PCI-32765), in Waldenstrom's Macroglobulinemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Waldenstrom's Macroglobulinemia
Keywords: Relapsed
Refractory
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
First posted: 2012-06-08
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate
timeFrame: 4 years
Secondary outcomes:
measure: Safety and Tolerability of PCI-32765
timeFrame: 4 years
measure: Determine Progression Free Survival
timeFrame: 6 years
measure: To Determine Time to Next Therapy (TTNT) of PCI-32765 in Symptomatic WM Patients With Relapsed/Refractory Disease
timeFrame: 6 years
measure: Major Response Rates
timeFrame: 4 years
measure: Very Good Partial Response Rate
timeFrame: 4 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Steven P Treon, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Treon SP, Meid K, Gustine J, Yang G, Xu L, Liu X, Patterson CJ, Hunter ZR, Branagan AR, Laubach JP, Ghobrial IM, Palomba ML, Advani R, Castillo JJ. Long-Term Follow-Up of Ibrutinib Monotherapy in Symptomatic, Previously Treated Patients With Waldenstrom Macroglobulinemia. J Clin Oncol. 2021 Feb 20;39(6):565-575. doi: 10.1200/JCO.20.00555. Epub 2020 Sep 15.
citation: Treon SP, Tripsas CK, Meid K, Warren D, Varma G, Green R, Argyropoulos KV, Yang G, Cao Y, Xu L, Patterson CJ, Rodig S, Zehnder JL, Aster JC, Harris NL, Kanan S, Ghobrial I, Castillo JJ, Laubach JP, Hunter ZR, Salman Z, Li J, Cheng M, Clow F, Graef T, Palomba ML, Advani RH. Ibrutinib in previously treated Waldenstrom's macroglobulinemia. N Engl J Med. 2015 Apr 9;372(15):1430-40. doi: 10.1056/NEJMoa1501548.