Safety of PCI-32765 in Chronic Lymphocytic Leukemia - Full Text View

Purpose

The purpose of this study is to establish the safety and efficacy of orally administered PCI-32765 in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.

Condition	Intervention	Phase
B-cell Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma	Drug: PCI-32765	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1b/2 Fixed-dose Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Chronic Lymphocytic Leukemia

Resource links provided by NLM:

Genetics Home Reference related topics: head and neck squamous cell carcinoma

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia Lymphoma

Drug Information available for: Ibrutinib

Genetic and Rare Diseases Information Center resources: B-cell Lymphomas Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Lymphosarcoma Squamous Cell Carcinoma of the Head and Neck

U.S. FDA Resources

Further study details as provided by Pharmacyclics:

Primary Outcome Measures:

Number of Participants With Treatment Emergent Adverse Events (AEs) [ Time Frame: From first dose to within 30 days of last dose of PCI-32765 ] [ Designated as safety issue: Yes ]
Number of participants who had experienced at least one treatment emergent AEs.

Secondary Outcome Measures:

Food Effect Cohort Assessments [ Time Frame: Fed was assessed on either Day 8 or Day 15 and Fasted was assessed on the remaining day as cross-over design. ] [ Designated as safety issue: No ]
Geometric mean ratio (Fed/Fasted) for PCI-32765 AUClast. The data were collected at 0, 0.5, 1, 2, 4, 6, 24 h post-dose. The AUClast was calculated from 0 up to 24 hours post-dose.
Progression Free Survival Rate at 24 Months [ Time Frame: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months). ] [ Designated as safety issue: No ]
Criteria for progression are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. progression defined as a 50% increase in lymph node size.
Percentage of Participants Achieving Response [ Time Frame: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months). ] [ Designated as safety issue: No ]
Response criteria are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. response requires 50% reduction in lymph node size.


Enrollment:	133
Study Start Date:	May 2010
Study Completion Date:	February 2013
Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: PCI-32765	Drug: PCI-32765 420 mg daily or 840 mg daily

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

FOR TREATMENT-NAIVE GROUP ONLY: Men and women ≥ 65 years of age with confirmed diagnosis of CLL/SLL, who require treatment per NCI or International Working Group guidelines 15-18
FOR RELAPSED/REFRACTORY GROUP ONLY: Men and women ≥ 18 years of age with a confirmed diagnosis of relapsed/refractory CLL/SLL following previous therapy(ie, failed ≥ 2 previous treatments for CLL/SLL and at least 1 regimen had to have had a purine analog [eg, fludarabine] for subjects with CLL)
FOR HIGH-RISK RELAPSED/ REFRACTORYGROUP ONLY: Men and women ≥ 18 years of age with a confirmed diagnosis of relapsed/refractory CLL/SLL with suboptimal response to chemoimmunotherapy, defined as progression of disease within 24 months of initiation of a regimen containing at least a nucleoside analogue or bendamustine in combination with a monoclonal antibody or failure to respond to such a regimen. (Note: a minimum of 2 cycles of chemoimmunotherapy required for eligibility)
ECOG performance status of ≤ 2
Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty

Exclusion Criteria:

Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for at least 2 years or which will not limit survival to < 2 years
Any immunotherapy, chemotherapy, radiotherapy, or experimental therapy within 4 weeks before first dose of study drug (corticosteroids for disease-related symptoms allowed but require 1-week washout before study drug administration)
Central nervous system (CNS) involvement by lymphoma
Major surgery within 4 weeks before first dose of study drug
Concomitant use of medicines known to cause QT prolongation or torsades de pointes
Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, and QTc > 470 msec
Lactating or pregnant

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01105247

Locations


United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, New York
New York Presbyterian Hosptial Cornell Med Center
New York, New York, United States, 10065
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
United States, Oregon
Willamette Valley Cancer Institute and Research Center
Springfield, Oregon, United States, 97477
United States, Tennessee
Sarah Cannon
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Texas Oncology - Tyler
Tyler, Texas, United States, 75702
United States, Vermont
University of Vermont and Fletcher Allen Health Care
Burlington, Vermont, United States, 05405
United States, Washington
Northwest Cancer Specialists, P.C.
Vancouver, Washington, United States, 98686
Yakima Valley Memorial
Yakima, Washington, United States, 98902

Sponsors and Collaborators

Pharmacyclics

Investigators


Study Director:	Danelle James, M.D., M.A.S	Pharmacyclics

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided by Pharmacyclics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

O'Brien S, Furman RR, Coutre SE, Sharman JP, Burger JA, Blum KA, Grant B, Richards DA, Coleman M, Wierda WG, Jones JA, Zhao W, Heerema NA, Johnson AJ, Izumi R, Hamdy A, Chang BY, Graef T, Clow F, Buggy JJ, James DF, Byrd JC. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014 Jan;15(1):48-58. doi: 10.1016/S1470-2045(13)70513-8. Epub 2013 Dec 10.

Dubovsky JA, Beckwith KA, Natarajan G, Woyach JA, Jaglowski S, Zhong Y, Hessler JD, Liu TM, Chang BY, Larkin KM, Stefanovski MR, Chappell DL, Frissora FW, Smith LL, Smucker KA, Flynn JM, Jones JA, Andritsos LA, Maddocks K, Lehman AM, Furman R, Sharman J, Mishra A, Caligiuri MA, Satoskar AR, Buggy JJ, Muthusamy N, Johnson AJ, Byrd JC. Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013 Oct 10;122(15):2539-49. doi: 10.1182/blood-2013-06-507947. Epub 2013 Jul 25.

Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, Grant B, Sharman JP, Coleman M, Wierda WG, Jones JA, Zhao W, Heerema NA, Johnson AJ, Sukbuntherng J, Chang BY, Clow F, Hedrick E, Buggy JJ, James DF, O'Brien S. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013 Jul 4;369(1):32-42. doi: 10.1056/NEJMoa1215637. Epub 2013 Jun 19. Erratum in: N Engl J Med. 2014 Feb 20;370(8):786.


Responsible Party:	Pharmacyclics
ClinicalTrials.gov Identifier:	NCT01105247 History of Changes
Other Study ID Numbers:	PCYC-1102-CA, PCI-32765
Study First Received:	April 13, 2010
Results First Received:	December 16, 2013
Last Updated:	February 13, 2014
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by Pharmacyclics:


PCI-32765 Lymphoma, B-Cell Leukemia, Lymphoid Leukemia, B-Cell Bruton's Tyrosine Kinase

Additional relevant MeSH terms:


Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphoma Immune System Diseases Immunoproliferative Disorders	Leukemia, B-Cell Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on February 26, 2015