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

Mantle Cell Lymphoma Clinical Trial

— PCYC-1104-CA  

Official title:

Multicenter Phase 2 Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Relapsed or Refractory Mantle Cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01236391
• Other study ID #: PCYC-1104-CA
• Secondary ID: PCI-32765
• Status: Completed
• Phase: Phase 2
• First received: October 18, 2010
• Last updated: August 24, 2015
• Start date: February 2011
• Est. completion date: January 2014

Study information

• Verified date: August 2015
• Source: Pharmacyclics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: National Health ServiceUnited Kingdom: Research Ethics CommitteeUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyGermany: Ethics CommissionGermany: Ministry of HealthPoland: Ethics CommitteePoland: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 115
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

Drug:
• PCI-32765
560 mg daily

Locations

Country	Name	City	State
Germany	Klinikum der Universitat Munchen - Campus Grosshadern	Munchen
Germany	Universitatsklinikum Ulm, Klinik fur Innere Medizin II	ULM
Poland	Oddzail Kliniczny Onkologil	Bydgoszcz
Poland	Malopolskie Centrum Medyczne	Krakow
Poland	MTZ Clinical Research Sp. z o.o.	Warsaw
United Kingdom	Centre for Experimental Cancer Medicine	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Southampton General Hospital	Southampton
United States	University of Virginia School of Medicine Hospital	Charlottesville	Virginia
United States	The Ohio Sate university	Columbus	Ohio
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Wisconsin	Madison	Wisconsin
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	Oregon Health & Science University	Portland	Oregon
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Pharmacyclics	Janssen Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Number of Participants With Treatment Emergent Adverse Events (AEs)	Number of participants who had experienced at least one treatment emergent AE	From first dose of PCI-32765 to within 30 days of last dose for each participant or until study closure	Yes
Secondary	PCI-32765 and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765	Area under the plasma concentration-time curve using data collected at 0, 1, 2, 4, 6-8, and 24 hours post dose (AUC0-24h)	Performed During the First Month of Receiving PCI-32765	No
Secondary	Mean Change From Baseline to Cycle 5 in EORTC QLQ-C30 Global Health Status Score	Mean change from baseline to Cycle 5 in the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) Global Health Status Score according to EORTC QLQ-C30 Scoring Manual (3rd Edition, 2001). For global health status, positive changes indicated better health status or functioning, and negative changes indicated worsening of health status or functioning. Scale scores range from 0 to 100. A change in 5 to 10 points in either direction represents a small change; 10 to 20 points represents a moderate change and greater than 20 points represents a large change.	From Baseline to Cycle 5 (Week 20)	No

External Links

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