Diffuse Large Cell B-lymphomaPhase 2NCT01325701
Safety and Efficacy Study of a BTK Inhibitor in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma
A Phase 2 study testing ibrutinib in people with Diffuse Large Cell B-lymphoma, run by Pharmacyclics LLC. at 15 sites in United States.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large Cell B-lymphoma
- What is being tested?
- ibrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 15 sitesUnited States
- Study dates
- May 2011to Oct 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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:
Show all 15Show fewer
- 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.
- 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.
- AST or ALT ≥ 3.0 x upper limit of normal (ULN)
- Creatinine > 2.0 x ULN
- Treatment Group 2 only: Hemoglobin < 8.0 g/dL
- 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.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
National Cancer Institute
Bethesda, Maryland, 20892-1203
The Ohio Sate university
Columbus, Ohio, 43210
Hackensack University Medical Center
Hackensack, New Jersey, 07601
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
UCLA Medical Center
Los Angeles, California, 90095
University of Wisconsin
Madison, Wisconsin, 53705
Long Island Jewish Medical Center
New Hyde Park, New York, 11042
New York University
New York, New York, 10016
Weill Medical College of Cornell University
New York, New York, 10021
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Mayo Clinic
Rochester, Minnesota, 55905
University of Rochester School of Medicine and Dentistry
Rochester, New York, 14642
Univerity of Washington
Seattle, Washington, 98109
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: A Multicenter, Open-label, Phase 2, Safety and Efficacy Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Subjects With Relapsed or Refractory or de Novo Diffuse Large B-cell Lymphoma (DLBCL)
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
- Diffuse Large Cell B-lymphoma
- Being tested
- ibrutinib
- Keywords
- PCI-32765, Lymphoma, B-Cell, Bruton's Tyrosine Kinase, Non Hodgkin's Lymphoma, Germinal Center B-Cell, Activated B-Cell
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, B-Cell, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ibrutinibDrug
Also called PCI-32765, Imbruvica
ibrutinib is an inhibitor of BTK
| Study group | Role | What they receive |
|---|---|---|
| PCI-32765: 560 mg | Experimental | Treatment Group 1: Subjects received 560 mg of ibrutinib once daily, on a continuous basis. Receives: Drug: ibrutinib |
| PCI-32765: 840 mg | Experimental | Treatment Group 2: Subjects received 840 mg of ibrutinib once daily, on a continuous basis. Receives: Drug: ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: The median follow up time on the study for all treated participants is 1.7 months (range 0.1- 32.3 months)
Secondary outcomes (2)
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.
Measured: 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
Measured: Performed during the first month of receiving study drug.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2011 (estimated)
- Study startMay 2011
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large Cell B-lymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharmacyclics LLC.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Darrin Beaupre, MD, Study director, Pharmacyclics LLC.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01325701
- Sponsor's protocol ID
- PCYC-1106-CA
- Other IDs
- PCI-32765
- Status last verified
- Mar 2017
- First submitted
- 2 Feb 2011
- Last updated
- 31 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
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
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label, Phase 2, Safety and Efficacy Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Subjects With Relapsed or Refractory or de Novo Diffuse Large B-cell Lymphoma (DLBCL)
- ClinicalTrials.gov ID
- NCT01325701
- Acronym / sponsor ID
- PCYC-1106-CA
- Conditions
- Diffuse Large Cell B-lymphoma
- Keywords
- PCI-32765, Lymphoma, B-Cell, Bruton's Tyrosine Kinase, Non Hodgkin's Lymphoma, Germinal Center B-Cell, Activated B-Cell
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Pharmacyclics LLC.Industry (pharma, biotech, devices)
- Study start
- May 2011
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 30 Mar 2011 (estimated)
- Results
- Posted 16 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PCI-32765: 560 mg | Experimental | Drug: ibrutinibTreatment Group 1: Subjects received 560 mg of ibrutinib once daily, on a continuous basis. |
| PCI-32765: 840 mg | Experimental | Drug: ibrutinibTreatment Group 2: Subjects received 840 mg of ibrutinib once daily, on a continuous basis. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ibrutinibAlso: PCI-32765, Imbruvicaibrutinib is an inhibitor of BTK | Drug | PCI-32765: 560 mg, PCI-32765: 840 mg |
Primary outcome
Percentage of Patients With an Overall Response to Study Drug
Time frame: The median follow up time on the study for all treated participants is 1.7 months (range 0.1- 32.3 months)
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.
2 secondary outcomes
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
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
Time frame: Performed during the first month of receiving study drug.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26193343Wilson 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Darrin Beaupre, MD study director
Pharmacyclics LLC.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ibrutinib in people with Diffuse Large Cell B-lymphoma, run by Pharmacyclics LLC. at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients With an Overall Response to Study Drug (time frame: The median follow up time on the study for all treated participants is 1.7 months (range 0.1- 32.3 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01325701, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2017.