CompletedNCT01105247Updated Mar 31, 2014Results posted

Safety of PCI-32765 in Chronic Lymphocytic Leukemia

A Phase 1/2 interventional study of PCI-32765 in B-cell Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, sponsored by Pharmacyclics LLC.. Completed at 10 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-03-31.

Sponsored by Pharmacyclics LLC. · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 133
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study 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 studied

B-cell Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma

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Keywords

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

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 133 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

Pharmacyclics LLC. is the lead sponsor of 54 studies on the registry; none are open to participants now.

Of its 10 completed or terminated interventional studies of FDA-regulated products, 9 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Single group
Masking: None (open label)
Enrollment: 133 participants (actual)

Study arms

Experimental
PCI-32765
Drug: PCI-32765

Interventions

DrugPCI-32765
420 mg daily or 840 mg daily

What researchers measure

Primary outcomes

Number of Participants With Treatment Emergent Adverse Events (AEs)
Number of participants who had experienced at least one treatment emergent AEs.
Time frame: From first dose to within 30 days of last dose of PCI-32765

Secondary outcomes

Food Effect Cohort Assessments
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.
Time frame: 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
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.
Time frame: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).
Percentage of Participants Achieving Response
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.
Time frame: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).

Results

Posted Mar 31, 2014

Participant flow

There are total 133 subjects enrolled however one subject never received treatment. Therefore, number of subjects "Started" the study is listed as 132 subjects.

Participant flow — Overall Study
Milestone	PCI-32765	Food Effect Cohort
Started	116	16
Completed	79	16
Not completed	37	0

Outcome measures

PrimaryNumber of Participants With Treatment Emergent Adverse Events (AEs)

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

Time frame:: From first dose to within 30 days of last dose of PCI-32765
Reported as:: Number · Participants

Number of Participants With Treatment Emergent Adverse Events (AEs)
Participants	PCI-32765	Food Effect
Number of Participants With Treatment Emergent Adverse Events (AEs)	116	11

SecondaryFood Effect Cohort Assessments

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.

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

Food Effect Cohort Assessments
Measure	Food Effect Cohort
Food Effect Cohort Assessments	1.65 (1.23 to 2.19)

SecondaryProgression Free Survival Rate at 24 Months

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.

Time frame:: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).
Reported as:: Number · Percentage of Participants

Progression Free Survival Rate at 24 Months
Percentage of Participants	Treatment Naive	Relapsed/ Refractory	Food- Effect
Progression Free Survival Rate at 24 Months	96.3 (76.5 to 99.5)	73.6 (60.2 to 83.1)	NA (NA to NA)

SecondaryPercentage of Participants Achieving Response

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.

Time frame:: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).
Reported as:: Number · Percentage of Participants

Percentage of Participants Achieving Response
Percentage of Participants	Treatment Naive	Relapsed/ Refractory	Food Effect
Percentage of Participants Achieving Response	71 (52 to 85.8)	75.3 (64.7 to 84)	56.3 (29.9 to 80.2)

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
PCI-32765	—	61/116 (52.6%)	116/116 (100%)
Food Effect	—	7/16 (43.8%)	16/16 (100%)

Most frequent serious events

Showing 10 of 82

Most frequent serious events
Event	PCI-32765	Food Effect
PneumoniaInfections and infestations	11/116	4/16
Bronchitis viralInfections and infestations	1/116	1/16
Staphylococcal bacteraemiaInfections and infestations	1/116	1/16
SyncopeNervous system disorders	0/116	1/16
Febrile neutropeniaBlood and lymphatic system disorders	5/116	0/16
Atrial fibrillationCardiac disorders	4/116	0/16
BacteraemiaInfections and infestations	4/116	0/16
CellulitisInfections and infestations	4/116	0/16
SinusitisInfections and infestations	4/116	0/16
SepsisInfections and infestations	3/116	0/16

Most frequent other events

Showing 10 of 119

Most frequent other events
Event	PCI-32765	Food Effect
DiarrhoeaGastrointestinal disorders	65/116	11/16
VomitingGastrointestinal disorders	22/116	11/16
FatigueGeneral disorders	38/116	4/16
Upper respiratory tract infectionInfections and infestations	37/116	4/16
ArthralgiaMusculoskeletal and connective tissue disorders	31/116	5/16
Oedema peripheralGeneral disorders	33/116	1/16
NauseaGastrointestinal disorders	31/116	2/16
ContusionInjury, poisoning and procedural complications	22/116	4/16
EpistaxisRespiratory, thoracic and mediastinal disorders	13/116	4/16
HeadacheNervous system disorders	22/116	4/16

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	PCI-32765	Food Effect Cohort	Total
<=18 years	0	0	0
Between 18 and 65 years	42	9	51
>=65 years	74	7	81

Sex: Female, Male
Sex: Female, Male(Participants)	PCI-32765	Food Effect Cohort	Total
Female	32	2	34
Male	84	14	98

Study locations

10 sites

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

References and documents

Publications

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. PubMed 32209572 ↗
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. PubMed 31196847 ↗
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. PubMed 29470582 ↗
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. PubMed 29437592 ↗
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. PubMed 26813675 ↗
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. PubMed 26182309 ↗
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. PubMed 25724156 ↗
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. PubMed 25381051 ↗
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. PubMed 24332241 ↗
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. PubMed 23886836 ↗
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. PubMed 23782158 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 31, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01105247
Lead sponsor: Pharmacyclics LLC.
Responsible party: Sponsor
First posted: Apr 16, 2010
Start date: May 2010
Primary completion: Dec 2012
Completion: Feb 2013
Results posted: Mar 31, 2014
Last update: Mar 31, 2014

Study contacts

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

study director · Pharmacyclics LLC.

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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