Safety of PCI-32765 in Chronic Lymphocytic Leukemia

NCT01105247 | Completed Phase 1 Results

• 2 other identifiers: PCYC-1102-CAPCI-32765
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

B-cell Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

  Number of participants who had experienced at least one treatment emergent AEs.

  From first dose to within 30 days of last dose of PCI-32765

Secondary Outcomes (3)

• Food Effect Cohort Assessments

  Fed was assessed on either Day 8 or Day 15 and Fasted was assessed on the remaining day as cross-over design.

• Progression Free Survival Rate at 24 Months

  The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).

• Percentage of Participants Achieving Response

  The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).

Study Arms (1)

PCI-32765

EXPERIMENTAL

Drug: PCI-32765

Interventions

PCI-32765 DRUG

420 mg daily or 840 mg daily

PCI-32765

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pharmacyclics LLC.: lead

Study Sites (10)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

New York Presbyterian Hosptial Cornell Med Center

New York, New York, 10065, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Willamette Valley Cancer Institute and Research Center

Springfield, Oregon, 97477, United States

Location

Sarah Cannon

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Oncology - Tyler

Tyler, Texas, 75702, United States

Location

University of Vermont and Fletcher Allen Health Care

Burlington, Vermont, 05405, United States

Location

Northwest Cancer Specialists, P.C.

Vancouver, Washington, 98686, United States

Location

Yakima Valley Memorial

Yakima, Washington, 98902, United States

Location

Related Publications (11)

• Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum K, Sharman JP, Wierda W, Zhao W, Heerema NA, Luan Y, Liu EA, Dean JP, O'Brien S. Ibrutinib Treatment for First-Line and Relapsed/Refractory Chronic Lymphocytic Leukemia: Final Analysis of the Pivotal Phase Ib/II PCYC-1102 Study. Clin Cancer Res. 2020 Aug 1;26(15):3918-3927. doi: 10.1158/1078-0432.CCR-19-2856. Epub 2020 Mar 24.

  PMID: 32209572 DERIVED

• Coutre SE, Byrd JC, Hillmen P, Barrientos JC, Barr PM, Devereux S, Robak T, Kipps TJ, Schuh A, Moreno C, Furman RR, Burger JA, O'Dwyer M, Ghia P, Valentino R, Chang S, Dean JP, James DF, O'Brien SM. Long-term safety of single-agent ibrutinib in patients with chronic lymphocytic leukemia in 3 pivotal studies. Blood Adv. 2019 Jun 25;3(12):1799-1807. doi: 10.1182/bloodadvances.2018028761.

  PMID: 31196847 DERIVED

• O'Brien SM, Jaglowski S, Byrd JC, Bannerji R, Blum KA, Fox CP, Furman RR, Hillmen P, Kipps TJ, Montillo M, Sharman J, Suzuki S, James DF, Chu AD, Coutre SE. Prognostic Factors for Complete Response to Ibrutinib in Patients With Chronic Lymphocytic Leukemia: A Pooled Analysis of 2 Clinical Trials. JAMA Oncol. 2018 May 1;4(5):712-716. doi: 10.1001/jamaoncol.2017.5604.

  PMID: 29470582 DERIVED

• O'Brien S, Furman RR, Coutre S, Flinn IW, Burger JA, Blum K, Sharman J, Wierda W, Jones J, Zhao W, Heerema NA, Johnson AJ, Luan Y, James DF, Chu AD, Byrd JC. Single-agent ibrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia: a 5-year experience. Blood. 2018 Apr 26;131(17):1910-1919. doi: 10.1182/blood-2017-10-810044. Epub 2018 Feb 2.

  PMID: 29437592 DERIVED

• Fraietta JA, Beckwith KA, Patel PR, Ruella M, Zheng Z, Barrett DM, Lacey SF, Melenhorst JJ, McGettigan SE, Cook DR, Zhang C, Xu J, Do P, Hulitt J, Kudchodkar SB, Cogdill AP, Gill S, Porter DL, Woyach JA, Long M, Johnson AJ, Maddocks K, Muthusamy N, Levine BL, June CH, Byrd JC, Maus MV. Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia. Blood. 2016 Mar 3;127(9):1117-27. doi: 10.1182/blood-2015-11-679134. Epub 2016 Jan 26.

  PMID: 26813675 DERIVED

• Maddocks KJ, Ruppert AS, Lozanski G, Heerema NA, Zhao W, Abruzzo L, Lozanski A, Davis M, Gordon A, Smith LL, Mantel R, Jones JA, Flynn JM, Jaglowski SM, Andritsos LA, Awan F, Blum KA, Grever MR, Johnson AJ, Byrd JC, Woyach JA. Etiology of Ibrutinib Therapy Discontinuation and Outcomes in Patients With Chronic Lymphocytic Leukemia. JAMA Oncol. 2015 Apr;1(1):80-7. doi: 10.1001/jamaoncol.2014.218.

  PMID: 26182309 DERIVED

• de Jong J, Sukbuntherng J, Skee D, Murphy J, O'Brien S, Byrd JC, James D, Hellemans P, Loury DJ, Jiao J, Chauhan V, Mannaert E. The effect of food on the pharmacokinetics of oral ibrutinib in healthy participants and patients with chronic lymphocytic leukemia. Cancer Chemother Pharmacol. 2015 May;75(5):907-16. doi: 10.1007/s00280-015-2708-9. Epub 2015 Feb 28.

  PMID: 25724156 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

• 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.

  PMID: 24332241 DERIVED

• 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.

  PMID: 23886836 DERIVED

• 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.

  PMID: 23782158 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Leukemia, Lymphoid; Leukemia, B-Cell

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma

Results Point of Contact

• Title: Danelle James
• Organization: Pharmacyclics

medinfo@pcyc.com

855-427-8846

Study Officials

• Danelle James, M.D., M.A.S

  Pharmacyclics LLC.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2010
• First Posted: April 16, 2010
• Study Start: May 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: February 1, 2013
• Last Updated: March 31, 2014
• Results First Posted: March 31, 2014

Record last verified: 2014-02

Locations

US (10)