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

NCT01236391 | Completed Phase 2 Results

• 2 other identifiers: PCYC-1104-CAPCI-32765
• Study Type: interventional
• Target: 115
• Locations: 4 countries
• Sites: 18

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.

Conditions

Mantle Cell Lymphoma

Keywords

Pharmacyclics; Mantle; Mantle Cell; Lymphoma; Non-Hodgkins; Bortezomib; Velcade; Naive; PCYC

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving Response

  The primary endpoint of the study was overall response rate (ORR), defined as the proportion of participants who achieved a best overall response of complete response (CR) or partial response (PR), according to the revised International Working Group Criteria for non-Hodgkin's lymphoma (Cheson et al, 2007), as assessed by the investigator. CR is a complete disappearance of all disease, no new lesions, lymph nodes must have regressed and be PET negative, spleen and liver should not be palpable and without nodules, and bone marrow must be negative. PR is a \>/= 50% decrease in the sum of the product of diameters of the target lesions, and \>/= 50% decrease of splenic and hepatic nodules from baseline, no new lesions and no increase in the size of liver, spleen or non-target lesions.

  The median follow-up time on study for all treated participants is 15.3 (range 1.9 - 22.3) months

Secondary Outcomes (3)

• Number of Participants With Treatment Emergent Adverse Events (AEs)

  From first dose of PCI-32765 to within 30 days of last dose for each participant or until study closure

• PCI-32765 and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765

  Performed During the First Month of Receiving PCI-32765

• Mean Change From Baseline to Cycle 5 in EORTC QLQ-C30 Global Health Status Score

  From Baseline to Cycle 5 (Week 20)

Study Arms (1)

Participants received PCI-32765 560 mg daily

EXPERIMENTAL

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

Drug: PCI-32765

Interventions

PCI-32765 DRUG

560 mg daily

Participants received PCI-32765 560 mg daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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:
• Absolute neutrophil count (ANC) \< 750 cells/mm3 (0.75 x 109/L) unless there is documented bone marrow involvement
• Platelet count \< 50,000 cells/mm3 (50 x 109/L) independent of transfusion support unless there is documented bone marrow involvement
• Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN)
• Creatinine \> 2.0 x ULN

Sponsors & Collaborators

• Pharmacyclics LLC.: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (18)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Cll Research and Treatment Program

New Hyde Park, New York, 11042, United States

Location

New York Presbyterian Hospital/Cornell Medical Center

New York, New York, 94305, United States

Location

The Ohio Sate university

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia School of Medicine Hospital

Charlottesville, Virginia, 22908, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Klinikum der Universitat Munchen - Campus Grosshadern

München, D - 81377, Germany

Location

Universitatsklinikum Ulm, Klinik fur Innere Medizin II

Ulm, 89081, Germany

Location

Oddzail Kliniczny Onkologil

Bydgoszcz, 85-796, Poland

Location

Malopolskie Centrum Medyczne

Krakow, 30-510, Poland

Location

MTZ Clinical Research Sp. z o.o.

Warsaw, 02-106, Poland

Location

Centre for Experimental Cancer Medicine

London, EC1M6BQ, United Kingdom

Location

Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 26059948 DERIVED

• 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.

  PMID: 25381051 DERIVED

• 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.

  PMID: 23782157 DERIVED

Related Links

• www.pharmacyclics.com

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Lymphoma

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr. Darrin Beaupre
• Organization: Pharmacyclics, Inc.

medinfo@pcyc.com

855-427-8846

Study Officials

• Darrin Beaupre, MD, PhD

  Pharmacyclics LLC.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2010
• First Posted: November 8, 2010
• Study Start: February 1, 2011
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: August 28, 2015
• Results First Posted: March 13, 2015

Record last verified: 2015-08

Locations

DE (2); GB (4); PL (3); US (9)