CompletedNCT01325701Updated Mar 31, 2017Results posted

Safety and Efficacy Study of a BTK Inhibitor in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma

A Phase 2 interventional study of ibrutinib in Diffuse Large Cell B-lymphoma, sponsored by Pharmacyclics LLC.. Completed at 15 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-03-31.

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

Phase: Phase 2
Study type: Interventional
Enrollment: 78
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

The purpose of this study is to evaluate the efficacy of ibrutinib (PCI-32765) in relapsed/refractory de novo activated B-cell (ABC) and germinal-cell B-Cell (GCB) Diffuse Large B-cell Lymphoma (DLBCL).

Read the detailed description

The primary objectives of this study were to evaluate the efficacy of ibrutinib administered at 560 mg once per day in relapsed or refractory de novo ABC and GCB DLBCL, and to evaluate the efficacy of ibrutinib administered at 840 mg once per day in relapsed or refractory de novo ABC DLBCL.

The secondary objective was to evaluate the safety and tolerability of a fixed daily oral dosing regimen of ibrutinib in relapsed/refractory de novo DLBCL.

Conditions studied

Diffuse Large Cell B-lymphoma

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Keywords

PCI-32765
Lymphoma, B-Cell
Bruton's Tyrosine Kinase
Non Hodgkin's Lymphoma
Germinal Center B-Cell
Activated B-Cell

In context

Lymphoma

5,579 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 78 is above the median of 40 across 4,509 interventional studies indexed under Lymphoma.

Browse Lymphoma 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

Men and women ≥ 18 years of age.
ECOG performance status ≤ 2.
Pathologically confirmed de novo DLBCL
Subjects must have available tissue for central pathology review to be eligible. Treatment Group 2: Subjects will be eligible if they have the non-GCB phenotype, as confirmed by Central IHC testing by the Hans method.
Relapsed or refractory disease, defined as either: 1) recurrence of disease after a CR, or 2) PR, SD, or progressive disease (PD) at completion of the treatment regimen preceding entry to the study (residual disease): Subjects must have previously received an appropriate first-line treatment regimen. Subjects who have not received HDT/ASCT must be ineligible for HDT/ASCT
Treatment Group 1: Subjects must have ≥ 1 measurable (> 2 cm in longest dimension) disease sites on CT scan. Treatment Group 2: Subjects must have ≥ 1 measurable (> 1.5 cm in longest dimension) disease sites on CT scan.

Exclusion criteria

Exclusion Criteria:

Transformed DLBCL or DLBCL with coexistent histologies (eg, FL or MALT).
Primary mediastinal (thymic) large B-cell lymphoma.
Known central nervous system lymphoma. In addition, for subjects in Treatment Group 2, known leptomeningeal involvement is exclusionary.
Certain exclusions on prior therapy
Major surgery within 2 weeks of first dose of study drug.
Any of the following laboratory abnormalities:
1. ANC \< 0.75 x 10\^9/L. Treatment Group 2: Eligible subjects must be independent of growth factor support for 7 days prior to the screening lab tests.
2. Platelet count \< 50 x 10\^9/L independent of transfusion support. Treatment Group 2 only: Eligible subjects must be independent of transfusion support for 7 days prior to the screening lab tests.
3. AST or ALT ≥ 3.0 x upper limit of normal (ULN)
4. Creatinine > 2.0 x ULN
5. Treatment Group 2 only: Hemoglobin \< 8.0 g/dL
6. Treatment Group 2 only: Total Bilirubin > 1.5 x ULN
Requires or has received anticoagulation treatment with warfarin or equivalent Vitamin K antagonists (eg, phenprocoumon)
Treatment Group 2: Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor
Treatment Group 2: Known bleeding diathesis, eg, von Willebrand's disease, hemophilia.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Single group
Masking: None (open label)
Enrollment: 78 participants (actual)

Study arms

Experimental
PCI-32765: 560 mg
Treatment Group 1: Subjects received 560 mg of ibrutinib once daily, on a continuous basis.
Drug: ibrutinib
Experimental
PCI-32765: 840 mg
Treatment Group 2: Subjects received 840 mg of ibrutinib once daily, on a continuous basis.
Drug: ibrutinib

Interventions

Drugibrutinib
ibrutinib is an inhibitor of BTK
Also known as: PCI-32765, Imbruvica

What researchers measure

Primary outcomes

Percentage of Patients With an Overall Response to Study Drug
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.
Time frame: The median follow up time on the study for all treated participants is 1.7 months (range 0.1- 32.3 months)

Secondary outcomes

Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Participants will be followed until progression of the disease or start of another anticancer treatment. The clinical database captured all AEs from baseline through end of treatment. Treatment Emergent AEs were collected pre-dose, at the beginning of each cycle and 30 days post last dose of study drug, unless related to study drug.
Time frame: Adverse events determined to be related to study drug are collected from first dose until study exit (approximately 3 years).
Ibrutinib and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765
Treatment Group 1 PK collection schedule: Cycle 1 Day 1: Pre-dose, 1, 2, 4, 7, and 24 hours post-dose Cycle 1 Day 8: Pre-dose, 1, 2, 4, 7, and 24 hours post-dose Cycle 1 Day 15: Pre-dose and 2 hours post-dose Cycle 1 Day 22: Pre-dose and 2 hours post-dose Treatment Group 2 PK collection schedule: Cycle 1 Day 8: Pre-dose, 1, 2, 4 and 7 hours post-dose Cycle 1 Day 15: Pre-dose and 2 hours post-dose Cycle 1 Day 22: Pre-dose and 2 hours post-dose Cycle 3 Day 1: Pre-dose, 1, 2, and 4 hours post-dose
Time frame: Performed during the first month of receiving study drug.

Results

Posted Feb 16, 2017

Limitations and caveats

PCI-32765:840 mg:8 subjects were enrolled and followed through their 1st response assessment. Due to a lack of positive responses observed, enrollment was terminated for futility. Response rate should not be generalized due to small sample size.

Participant flow

Participant flow — Overall Study
Milestone	PCI-32765: 560 mg	PCI-32765: 840 mg
Started	70	8
Completed	49	5
Not completed	21	3
Withdrew: Adverse event	12	0
Withdrew: Protocol violation	1	0
Withdrew: Physician decision	2	2
Withdrew: Withdrawal by subject	2	1
Withdrew: Rollerover extension study	4	0

Outcome measures

PrimaryPercentage of Patients With an Overall Response to Study Drug

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.

Time frame:: The median follow up time on the study for all treated participants is 1.7 months (range 0.1- 32.3 months)
Reported as:: Number · percentage of participants

Percentage of Patients With an Overall Response to Study Drug
percentage of participants	PCI-32765: 560 mg	PCI-32765: 840 mg
Percentage of Patients With an Overall Response to Study Drug	24.3	12.5

SecondaryNumber of Patients With Adverse Events as a Measure of Safety and Tolerability

Participants will be followed until progression of the disease or start of another anticancer treatment. The clinical database captured all AEs from baseline through end of treatment. Treatment Emergent AEs were collected pre-dose, at the beginning of each cycle and 30 days post last dose of study drug, unless related to study drug.

Time frame:: Adverse events determined to be related to study drug are collected from first dose until study exit (approximately 3 years).
Reported as:: Number · participants

Number of Patients With Adverse Events as a Measure of Safety and Tolerability
participants	PCI-32765: 560 mg	PCI-32765: 840 mg
Number of Patients With Adverse Events as a Measure of Safety and Tolerability	70	8

SecondaryIbrutinib and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765

Treatment Group 1 PK collection schedule: Cycle 1 Day 1: Pre-dose, 1, 2, 4, 7, and 24 hours post-dose Cycle 1 Day 8: Pre-dose, 1, 2, 4, 7, and 24 hours post-dose Cycle 1 Day 15: Pre-dose and 2 hours post-dose Cycle 1 Day 22: Pre-dose and 2 hours post-dose Treatment Group 2 PK collection schedule: Cycle 1 Day 8: Pre-dose, 1, 2, 4 and 7 hours post-dose Cycle 1 Day 15: Pre-dose and 2 hours post-dose Cycle 1 Day 22: Pre-dose and 2 hours post-dose Cycle 3 Day 1: Pre-dose, 1, 2, and 4 hours post-dose

Time frame:: Performed during the first month of receiving study drug.
Reported as:: Mean · ng*h/mL

Ibrutinib and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765
ng*h/mL	PCI-32765: 560 mg	PCI-32765: 840 mg
PCI-32765 - Day 8	1285 ± 971	1337 ± 1556
PCI-45227 (Metabolite)- Day 8	1485 ± 948	1671 ± 1147

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
PCI-32765: 560 mg	—	40/70 (57.1%)	70/70 (100%)
PCI-32765: 840 mg	—	3/8 (37.5%)	8/8 (100%)

Most frequent serious events

Showing 10 of 49

Most frequent serious events
Event	PCI-32765: 560 mg	PCI-32765: 840 mg
DehydrationMetabolism and nutrition disorders	0/70	2/8
Diffuse large B-cell lymphomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)	5/70	2/8
Febrile neutropeniaBlood and lymphatic system disorders	1/70	1/8
Hypercalcaemia of malignancyEndocrine disorders	0/70	1/8
PancreatitisGastrointestinal disorders	0/70	1/8
Non-cardiac chest painGeneral disorders	0/70	1/8
PneumoniaInfections and infestations	7/70	1/8
Enterobacter sepsisInfections and infestations	0/70	1/8
HypotensionVascular disorders	0/70	1/8
Respiratory failureRespiratory, thoracic and mediastinal disorders	4/70	0/8

Most frequent other events

Showing 10 of 251

Most frequent other events
Event	PCI-32765: 560 mg	PCI-32765: 840 mg
NauseaGastrointestinal disorders	24/70	4/8
FatigueGeneral disorders	30/70	0/8
DiarrhoeaGastrointestinal disorders	28/70	3/8
Alanine aminotransferase increasedInvestigations	6/70	3/8
InsomniaPsychiatric disorders	7/70	3/8
AnaemiaBlood and lymphatic system disorders	20/70	1/8
Non-cardiac chest painGeneral disorders	0/70	2/8
Aspartate aminotransferase increasedInvestigations	7/70	2/8
HypoalbuminaemiaMetabolism and nutrition disorders	11/70	2/8
DehydrationMetabolism and nutrition disorders	5/70	2/8

Baseline characteristics

A total of 78 subjects were enrolled: 70 in PCI-32765: 560 mg , and 8 in PCI-32765: 840 mg . All subjects received at least 1 dose of study drug.

Age, Categorical
Age, Categorical(Participants)	PCI-32765: 560 mg	PCI-32765: 840 mg	Total
<=18 years	0	0	0
Between 18 and 65 years	38	4	42
>=65 years	32	4	36

Age, Continuous
Age, Continuous(Years)	PCI-32765: 560 mg	PCI-32765: 840 mg	Total
Mean	62.5 ± 13.40	64.4 ± 13.96	62.7 ± 13.38

Sex: Female, Male
Sex: Female, Male(Participants)	PCI-32765: 560 mg	PCI-32765: 840 mg	Total
Female	20	2	22
Male	50	6	56

Region of Enrollment
Region of Enrollment(participants)	PCI-32765: 560 mg	PCI-32765: 840 mg	Total
United States	70	8	78

Study locations

15 sites

UCLA Medical Center
Los Angeles, California 90095, United States
Stanford University School of Medicine
Stanford, California 94305, United States
National Cancer Institute
Bethesda, Maryland 20892-1203, United States
Mayo Clinic
Rochester, Minnesota 55905, United States
University of Nebraska Medical Center
Omaha, Nebraska 68198, United States
Hackensack University Medical Center
Hackensack, New Jersey 07601, United States
Long Island Jewish Medical Center
New Hyde Park, New York 11042, United States
New York University
New York, New York 10016, United States
Weill Medical College of Cornell University
New York, New York 10021, United States
Memorial Sloan-Kettering Cancer Center
New York, New York 10065, United States
University of Rochester School of Medicine and Dentistry
Rochester, New York 14642, United States
The Ohio Sate university
Columbus, Ohio 43210, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas 77030, United States
Univerity of Washington
Seattle, Washington 98109, United States
University of Wisconsin
Madison, Wisconsin 53705, United States

References and documents

Publications

Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, Lih CJ, Williams PM, Shaffer AL, Gerecitano J, de Vos S, Goy A, Kenkre VP, Barr PM, Blum KA, Shustov A, Advani R, Fowler NH, Vose JM, Elstrom RL, Habermann TM, Barrientos JC, McGreivy J, Fardis M, Chang BY, Clow F, Munneke B, Moussa D, Beaupre DM, Staudt LM. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015 Aug;21(8):922-6. doi: 10.1038/nm.3884. Epub 2015 Jul 20. PubMed 26193343 ↗

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 31, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01325701
Lead sponsor: Pharmacyclics LLC.
Responsible party: Sponsor
First posted: Mar 30, 2011
Start date: May 2011
Primary completion: Oct 2014
Completion: Oct 2014
Results posted: Feb 16, 2017
Last update: Mar 31, 2017

Study contacts

Darrin Beaupre, MD

study director · Pharmacyclics LLC.

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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