Safety of PCI-32765 in Chronic Lymphocytic Leukemia

NCT ID: NCT01105247

Last Updated: 2014-03-31

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

133 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-05-31

Study Completion Date

2013-02-28

Brief Summary

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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.

Detailed Description

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Conditions

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B-cell Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma

Keywords

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PCI-32765

Group Type EXPERIMENTAL

PCI-32765

Intervention Type DRUG

420 mg daily or 840 mg daily

Interventions

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PCI-32765

420 mg daily or 840 mg daily

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. 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
2. 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)
3. 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)
4. ECOG performance status of ≤ 2
5. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty

Exclusion Criteria

1. 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
2. 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)
3. Central nervous system (CNS) involvement by lymphoma
4. Major surgery within 4 weeks before first dose of study drug
5. Concomitant use of medicines known to cause QT prolongation or torsades de pointes
6. Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, and QTc \> 470 msec
7. Lactating or pregnant
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pharmacyclics LLC.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Danelle James, M.D., M.A.S

Role: STUDY_DIRECTOR

Pharmacyclics LLC.

Locations

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Stanford University School of Medicine

Stanford, California, United States

Site Status

New York Presbyterian Hosptial Cornell Med Center

New York, New York, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Willamette Valley Cancer Institute and Research Center

Springfield, Oregon, United States

Site Status

Sarah Cannon

Nashville, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Texas Oncology - Tyler

Tyler, Texas, United States

Site Status

University of Vermont and Fletcher Allen Health Care

Burlington, Vermont, United States

Site Status

Northwest Cancer Specialists, P.C.

Vancouver, Washington, United States

Site Status

Yakima Valley Memorial

Yakima, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 32209572 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31196847 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29470582 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29437592 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26813675 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26182309 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25724156 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25381051 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24332241 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23886836 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23782158 (View on PubMed)

Related Links

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Other Identifiers

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PCI-32765

Identifier Type: OTHER

Identifier Source: secondary_id

PCYC-1102-CA

Identifier Type: -

Identifier Source: org_study_id