Marginal Zone LymphomaPhase 2NCT01980628
Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed/Refractory Marginal Zone Lymphoma
A Phase 2 study testing ibrutinib in people with Marginal Zone Lymphoma and B-cell Lymphoma, run by Pharmacyclics LLC. at 25 sites in 5 countries.
Trial summary
Phase 2, open-label, non-randomized, monotherapy study to evaluate the safety and efficacy of ibrutinib in subject with relapsed/refractory Marginal Zone Lymphoma (MZL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Marginal Zone Lymphoma, B-cell Lymphoma
- What is being tested?
- ibrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 25 sitesin 5 countries
- Study dates
- Dec 2013to 2 Oct 2017
- 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
- Histologically documented marginal zone lymphoma including splenic, nodal, and extranodal sub-types; subjects with splenic MZL must have an additional measurable lesion, nodal or extranodal, as described in inclusion criteria 5
- Previously received one or more lines of therapy including at least one CD20-directed regimen (either as monotherapy or as chemoimmunotherapy) with documented failure to achieve at least PR or documented PD after, the most recent systemic treatment regimen
- Men and women ≥18 years of age
- ECOG performance status of ≤2
- ≥1 measurable lesion site on CT scan (>1.5 cm in longest dimension). Lesions in anatomical locations (such as extremities or soft tissue lesions) that are not well visualized by CT may be measured by MRI instead. (Subjects with spleen-only disease are considered as not having measurable disease.)
- Life expectancy of >3 months, in the opinion of the investigator
Who cannot join
- Medically apparent CNS lymphoma or leptomeningeal disease
- History of other malignancies except adequately treated non melanoma skin cancer, curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for ≥2 years
- History of allogeneic stem-cell (or other organ) transplantation
- Any chemotherapy, anticancer antibodies, or other systemic anticancer therapy within 21 days of the first dose of study drug
- Any external beam radiation therapy within 6 weeks prior to the first dose of the study drug
- Concurrent use of warfarin or other vitamin K antagonists
Show all 10Show fewer
- Concurrent use of a strong CYP3A inhibitor. Subjects who have received a strong CYP3A inhibitor prior to entering the study must have discontinued therapy for at least 5 half lives of the prohibited medication.
- Recent infection requiring IV anti-infective treatment that was completed ≤14 days before the first dose of study drug
- Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to CTCAE Grade 0 or 1, or to the levels dictated in the eligibility criteria with the exception of alopecia
- Inadequate organ function as defined on laboratory tests
Trial locations and contacts
25 sites in 5 countries.
25 sites in 5 countries
United States13 sites
Site Reference ID/Investigator# 033
Atlanta, Georgia, 30322
Site Reference ID/Investigator# 370
Chicago, Illinois, 60611
Site Reference ID/Investigator# 195
Detroit, Michigan, 48202
Site Reference ID/Investigator# 047
Duarte, California, 91010
Site Reference ID/Investigator# 220
Hershey, Pennsylvania, 17033
Site Reference ID/Investigator# 350
New Hyde Park, New York, 11042
Site Reference ID/Investigator# 745
New York, New York, 08724
Site Reference ID/Investigator # 200
New York, New York, 10065
Site Reference ID/Investigator # 407
New York, New York, 10065
Site Reference ID/Investigator# 377
Santa Monica, California, 90095
Site Reference ID/Investigator# 348
Seattle, Washington, 98109
Site Reference ID/Investigator# 837
Tucson, Arizona, 85719
Site Reference ID/Investigator# 763
West Palm Beach, Florida, 33401
France7 sites
Site Reference ID/Investigator# 749
La Roche-sur-Yon, Pays de la Loire Region
Site Reference ID/Investigator# 750
Lille, Hauts-de-France
Site Reference ID/Investigator# 736
Nantes, Pays de la Loire Region
Site Reference ID/Investigator# 735
Paris, Île-de-France Region
Site Reference ID/Investigator# 142
Pierre-Bénite, Auvergne-Rhône-Alpes
Site Reference ID/Investigator# 742
Rennes
Site Reference ID/Investigator# 737
Rouen, Haute-normandie
United Kingdom3 sites
Site Reference ID/Investigator# 030
Manchester, England
Site Reference ID/Investigator# 814
Oxford, England
Site Reference ID/Investigator# 368
Plymouth, England
About this study
Official title: A Multicenter, Open-Label, Phase 2 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Subjects With Relapsed/Refractory Marginal Zone Lymphoma
Phase 2, open-label, non-randomized, monotherapy study to evaluate the safety and efficacy of ibrutinib in subject with relapsed/refractory Marginal Zone Lymphoma (MZL).
Read the detailed description
Ibrutinib is a first-in-class, potent, orally administered covalent inhibitor of Bruton's tyrosine kinase (BTK). Inhibition of BTK blocks downstream B-cell receptor (BCR) signaling pathways and thus prevents B-cell proliferation. In vitro, ibrutinib inhibits purified BTK and selected members of the kinase family with 10-fold specificity compared with non-BTK kinases. Phase 1 and 2 studies of ibrutinib in B-cell malignancies demonstrate modest toxicity and significant single agent activity in a variety of B-cell malignancies, including NHL.
- Conditions
- Marginal Zone Lymphoma, B-cell Lymphoma
- Being tested
- ibrutinib
- Keywords
- MZL, NHL, SMZL, NMZL, MALT
- Medical subject headings
- Lymphoma, B-Cell, Marginal Zone, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ibrutinibDrug
Also called PCI-32765
| Study group | Role | What they receive |
|---|---|---|
| ibrutinib | Experimental | ibrutinib capsules: 560 mg once daily Receives: Drug: ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR (Overall Response Rate)
ORR is defined as the proportion of subjects who achieved complete response (CR), partial response (PR). Response criteria are as outlined in the International Working Group Criteria for NHL, Cheson (2007), with disease assessments performed by an independent review committee (IRC).
Per Cheson:
CR is defined as disappearance of all evidence of disease. PR is defined as regression of measurable disease and no new sites.
Measured: Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.
Secondary outcomes (1)
DOR (Duration of Response)
The DOR analyses is performed on the subset of subjects that achieve CR or PR as determined by IRC. DOR is calculated as the duration of time from the date of first response to the date of progression or death due to any cause.
Measured: Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2013 (estimated)
- Study startDec 2013
- Primary completionJul 2016
- Study completion2 Oct 2017
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 (2)Papers the sponsor has linked to this study.
- Other trials for Marginal Zone 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharmacyclics LLC.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Janssen Research & Development, LLC
- Responsible party
- Sponsor
- Investigators
- Isaiah Dimery, MD, Study director, Pharmacyclics LLC.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01980628
- Sponsor's protocol ID
- PCYC-1121-CA
- Status last verified
- Oct 2019
- First submitted
- 29 Oct 2013
- Last updated
- 16 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Noy A, de Vos S, Coleman M, Martin P, Flowers CR, Thieblemont C, Morschhauser F, Collins GP, Ma S, Peles S, Smith SD, Barrientos JC, Chong E, Wu S, Cheung LW, Kwei K, Hauns B, Arango-Hisijara I, Chen R. Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis. Blood Adv. 2020 Nov 24;4(22):5773-5784. doi: 10.1182/bloodadvances.2020003121.
PubMed 33227125Noy A, de Vos S, Thieblemont C, Martin P, Flowers CR, Morschhauser F, Collins GP, Ma S, Coleman M, Peles S, Smith S, Barrientos JC, Smith A, Munneke B, Dimery I, Beaupre DM, Chen R. Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood. 2017 Apr 20;129(16):2224-2232. doi: 10.1182/blood-2016-10-747345. Epub 2017 Feb 6.
PubMed 28167659
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-Label, Phase 2 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Subjects With Relapsed/Refractory Marginal Zone Lymphoma
- ClinicalTrials.gov ID
- NCT01980628
- Acronym / sponsor ID
- PCYC-1121-CA
- Conditions
- Marginal Zone Lymphoma, B-cell Lymphoma
- Keywords
- MZL, NHL, SMZL, NMZL, MALT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Pharmacyclics LLC.Industry (pharma, biotech, devices)
- Collaborators
- Janssen Research & Development, LLC
- Study start
- Dec 2013
- Primary completion
- Jul 2016 (actual)
- Study completion
- 2 Oct 2017 (actual)
- First posted
- 11 Nov 2013 (estimated)
- Results
- Posted 10 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 2, open-label, non-randomized, monotherapy study to evaluate the safety and efficacy of ibrutinib in subject with relapsed/refractory Marginal Zone Lymphoma (MZL).
Detailed description
Ibrutinib is a first-in-class, potent, orally administered covalent inhibitor of Bruton's tyrosine kinase (BTK). Inhibition of BTK blocks downstream B-cell receptor (BCR) signaling pathways and thus prevents B-cell proliferation. In vitro, ibrutinib inhibits purified BTK and selected members of the kinase family with 10-fold specificity compared with non-BTK kinases. Phase 1 and 2 studies of ibrutinib in B-cell malignancies demonstrate modest toxicity and significant single agent activity in a variety of B-cell malignancies, including NHL.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ibrutinib | Experimental | Drug: ibrutinibibrutinib capsules: 560 mg once daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically documented marginal zone lymphoma including splenic, nodal, and extranodal sub-types; subjects with splenic MZL must have an additional measurable lesion, nodal or extranodal, as described in inclusion criteria 5
- Previously received one or more lines of therapy including at least one CD20-directed regimen (either as monotherapy or as chemoimmunotherapy) with documented failure to achieve at least PR or documented PD after, the most recent systemic treatment regimen
- Men and women ≥18 years of age
- ECOG performance status of ≤2
- ≥1 measurable lesion site on CT scan (>1.5 cm in longest dimension). Lesions in anatomical locations (such as extremities or soft tissue lesions) that are not well visualized by CT may be measured by MRI instead. (Subjects with spleen-only disease are considered as not having measurable disease.)
Key exclusion criteria (10 listed)
- Medically apparent CNS lymphoma or leptomeningeal disease
- History of other malignancies except adequately treated non melanoma skin cancer, curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for ≥2 years
- History of allogeneic stem-cell (or other organ) transplantation
- Any chemotherapy, anticancer antibodies, or other systemic anticancer therapy within 21 days of the first dose of study drug
- Any external beam radiation therapy within 6 weeks prior to the first dose of the 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 | Drug | ibrutinib |
Primary outcome
ORR (Overall Response Rate)
Time frame: Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.
ORR is defined as the proportion of subjects who achieved complete response (CR), partial response (PR). Response criteria are as outlined in the International Working Group Criteria for NHL, Cheson (2007), with disease assessments performed by an independent review committee (IRC). Per Cheson: CR is defined as disappearance of all evidence of disease. PR is defined as regression of measurable disease and no new sites.
1 secondary outcome
DOR (Duration of Response)
Time frame: Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33227125Noy A, de Vos S, Coleman M, Martin P, Flowers CR, Thieblemont C, Morschhauser F, Collins GP, Ma S, Peles S, Smith SD, Barrientos JC, Chong E, Wu S, Cheung LW, Kwei K, Hauns B, Arango-Hisijara I, Chen R. Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis. Blood Adv. 2020 Nov 24;4(22):5773-5784. doi: 10.1182/bloodadvances.2020003121.
- Derived from this study: PubMed 28167659Noy A, de Vos S, Thieblemont C, Martin P, Flowers CR, Morschhauser F, Collins GP, Ma S, Coleman M, Peles S, Smith S, Barrientos JC, Smith A, Munneke B, Dimery I, Beaupre DM, Chen R. Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood. 2017 Apr 20;129(16):2224-2232. doi: 10.1182/blood-2016-10-747345. Epub 2017 Feb 6.
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Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma
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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.
Isaiah Dimery, MD study director
Pharmacyclics LLC.
25 sites in 5 countries: 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 Marginal Zone Lymphoma and B-cell Lymphoma, run by Pharmacyclics LLC. at 25 sites in 5 countries.
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 10 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 16 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, France, United Kingdom, Belgium, Germany. 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 10 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?
ORR (Overall Response Rate) (time frame: Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 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 NCT01980628, which also lists 2 linked publications.
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 16 Oct 2019.