Clinical trial NCT01236391: Safety and Efficacy of PCI-32765 in Participants With Relapsed/Refractory Mantle Cell Lymphoma (MCL)
Official title: Multicenter Phase 2 Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Relapsed or Refractory Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mantle Cell Lymphoma
Keywords: Pharmacyclics
Mantle
Mantle Cell
Lymphoma
Non-Hodgkins
Bortezomib
Velcade
Naive
PCYC
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
Collaborators: name: Janssen Pharmaceuticals
First posted: 2010-11-08
Enrollment: 115
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: 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.

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)

Major 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

Primary outcomes:
measure: Percentage of Participants Achieving Response
timeFrame: The median follow-up time on study for all treated participants is 15.3 (range 1.9 - 22.3) months
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (AEs)
timeFrame: From first dose of PCI-32765 to within 30 days of last dose for each participant or until study closure
measure: PCI-32765 and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765
timeFrame: Performed During the First Month of Receiving PCI-32765
measure: Mean Change From Baseline to Cycle 5 in EORTC QLQ-C30 Global Health Status Score
timeFrame: From Baseline to Cycle 5 (Week 20)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Hyde Park
country: United States
facility: Cll Research and Treatment Program
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital/Cornell Medical Center
state: New York
city: Columbus
country: United States
facility: The Ohio Sate university
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia School of Medicine Hospital
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Munchen
country: Germany
facility: Klinikum der Universitat Munchen - Campus Grosshadern
city: ULM
country: Germany
facility: Universitatsklinikum Ulm, Klinik fur Innere Medizin II
city: Bydgoszcz
country: Poland
facility: Oddzail Kliniczny Onkologil
city: Krakow
country: Poland
facility: Malopolskie Centrum Medyczne
city: Warsaw
country: Poland
facility: MTZ Clinical Research Sp. z o.o.
city: London
country: United Kingdom
facility: Centre for Experimental Cancer Medicine
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Pharmacyclics LLC.
name: Darrin Beaupre, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.