Safety and Efficacy of PCI-32765 in Participants With Relapsed/Refractory Mantle Cell Lymphoma (MCL)

NCT ID: NCT01236391

Last Updated: 2015-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2014-01-31

Brief Summary

The primary objective of this study was to evaluate the efficacy of ibrutinib in participants with relapsed or refractory MCL.

The secondary objective was to evaluate the safety of a fixed daily dosing regimen (560 mg daily) of PCI-32765 in this population.

Detailed Description

This is a Phase 2, open-label, nonrandomized, multicenter, monotherapy study in subjects with histologically documented MCL who have relapsed after ≥ 1 (but not > 5) prior treatment regimens. All subjects meeting eligibility criteria will receive PCI-32765 capsules at a dosage of 560 mg/day once daily for a 28-day cycle until disease progression, unacceptable toxicity, or enrollment in a long-term extension study, whichever occurs earlier.

Conditions

Mantle Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Participants received PCI-32765 560 mg daily

Participants were enrolled and received 560 mg/day dose, stratified into 2 groups based on prior bortezomib exposure.

Group Type: EXPERIMENTAL

PCI-32765

Intervention Type: DRUG

560 mg daily

Interventions

PCI-32765

560 mg daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Men and women ≥ 18 years of age
• ECOG performance status of ≤ 2
• Pathologically confirmed MCL, with documentation of either overexpression of cyclin D1 or t(11;14), and measurable disease on cross sectional imaging that is ≥ 2 cm in the longest diameter and measurable in 2 perpendicular dimensions
• Documented failure to achieve at least partial response (PR) with, or documented disease progression disease after, the most recent treatment regimen
• At least 1, but no more than 5, prior treatment regimens for MCL (Note: Subjects having received ≥2 cycles of prior treatment with bortezomib, either as a single agent or as part of a combination therapy regimen, will be considered to be bortezomib-exposed.)
• Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations)

Exclusion Criteria

• Prior chemotherapy within 3 weeks, nitrosoureas within 6 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy within 3 weeks, or major surgery within 2 weeks of first dose of study drug
• Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of PCI-32765 capsules, or put the study outcomes at undue risk
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
• Any of the following laboratory abnormalities:

1. Absolute neutrophil count (ANC) < 750 cells/mm3 (0.75 x 109/L) unless there is documented bone marrow involvement

2. Platelet count < 50,000 cells/mm3 (50 x 109/L) independent of transfusion support unless there is documented bone marrow involvement

3. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN)

4. Creatinine > 2.0 x ULN

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Pharmacyclics LLC.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Darrin Beaupre, MD, PhD

Role: STUDY_DIRECTOR

Pharmacyclics LLC.

Locations

Stanford University School of Medicine

Stanford, California, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Cll Research and Treatment Program

New Hyde Park, New York, United States

New York Presbyterian Hospital/Cornell Medical Center

New York, New York, United States

The Ohio Sate university

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

MD Anderson Cancer Center

Houston, Texas, United States

University of Virginia School of Medicine Hospital

Charlottesville, Virginia, United States

University of Wisconsin

Madison, Wisconsin, United States

Klinikum der Universitat Munchen - Campus Grosshadern

München, , Germany

Universitatsklinikum Ulm, Klinik fur Innere Medizin II

Ulm, , Germany

Oddzail Kliniczny Onkologil

Bydgoszcz, , Poland

Malopolskie Centrum Medyczne

Krakow, , Poland

MTZ Clinical Research Sp. z o.o.

Warsaw, , Poland

Centre for Experimental Cancer Medicine

London, , United Kingdom

Christie Hospital

Manchester, , United Kingdom

Derriford Hospital

Plymouth, , United Kingdom

Southampton General Hospital

Southampton, , United Kingdom

Countries

United States; Germany; Poland; United Kingdom

References

Wang ML, Blum KA, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Zhang L, Baher L, Cheng M, Lee D, Beaupre DM, Rule S. Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results. Blood. 2015 Aug 6;126(6):739-45. doi: 10.1182/blood-2015-03-635326. Epub 2015 Jun 9.

Reference Type: DERIVED

PMID: 26059948 (View on PubMed)

Marostica E, Sukbuntherng J, Loury D, de Jong J, de Trixhe XW, Vermeulen A, De Nicolao G, O'Brien S, Byrd JC, Advani R, McGreivy J, Poggesi I. Population pharmacokinetic model of ibrutinib, a Bruton tyrosine kinase inhibitor, in patients with B cell malignancies. Cancer Chemother Pharmacol. 2015 Jan;75(1):111-21. doi: 10.1007/s00280-014-2617-3. Epub 2014 Nov 8.

Reference Type: DERIVED

PMID: 25381051 (View on PubMed)

Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Li L, Zhang L, Newberry K, Ou Z, Cheng N, Fang B, McGreivy J, Clow F, Buggy JJ, Chang BY, Beaupre DM, Kunkel LA, Blum KA. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013 Aug 8;369(6):507-16. doi: 10.1056/NEJMoa1306220. Epub 2013 Jun 19.

Reference Type: DERIVED

PMID: 23782157 (View on PubMed)

Related Links

http://www.pharmacyclics.com

www.pharmacyclics.com

Other Identifiers

PCI-32765

Identifier Type: OTHER

Identifier Source: secondary_id

PCYC-1104-CA

Identifier Type: -

Identifier Source: org_study_id