- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02542514
Study of Ibrutinib in Patients With Relapsed or Refractory Primary Central Nervous Lymphoma or Intraocular Lymphoma (iLOC)
April 6, 2022 updated by: The Lymphoma Academic Research Organisation
Phase II Study of Ibrutinib in Patients With Relapsed or Refractory Primary Central Nervous Lymphoma or Intraocular Lymphoma
The study is an open label, prospective, multicenter, phase II study which aims to define ibrutinib efficacy in patients with relapsed or refractory primary central nervous lymphoma (PCNSL) or intraocular lymphoma (IOL) as measured by the disease control (DC) rate (complete response (CR) + uncertain complete response (Ru) + partial response (PR) stabilized disease (SD)) after 2 cycles of treatment according to International study group for PCNSL (IPCG) criteria.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
52
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Clermont Ferrand, France
- Chu D'Estaing
-
Grenoble, France
- Chu de Grenoble
-
Lille, France
- CHRU de LILLE - Claude Huriez
-
Lyon, France
- Centre Léon Bérard
-
Paris, France
- CHU de la Pitié Salpêtrière
-
Paris, France
- CHU de la Timone
-
Rennes, France
- CHU de Rennes
-
Rouen, France
- Centre Henri Becquerel
-
Saint-Cloud, France
- Hôpital René Huguenin Institut Curie
-
Vandoeuvre les Nancy, France
- CHU Brabois
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Histologically confirmed diagnosis of PCNSL or cytologically proven diagnosis of IOL or lymphomatous meningitis of B-cell type. In case of CNS lymphoma relapse or refractory PCNSL, cerebral biopsies are not required if imaging reveals typical images of PCNSL. In case of isolated IOL relapse, vitrectomy is not required if i) vitrectomy was part of the initial diagnosis workout, and ii) ocular examination and dosage of IL-10 in the anterior chamber of the eye performed at relapse or progression are highly in favour of IOL relapse (> 50 pg/ml in aqueous humor or 400 pg/ml in vitreous).
- Aged 18 years and older.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
- Life expectancy ≥ 3 months.
- No more than 4 lines of anti-cancer treatment received.
- Patients must have recovered within 28 days to a grade ≤ 1 from all toxicities related to prior treatments.
- Adequate Laboratory Parameters within 14 days:
- Measurable PCNSL as diagnosed on MRI
- Highly effective method of birth control during and after the study consistent. Men must agree to not donate sperm during and after the study. These restrictions apply for 1 year after the last dose of study drug.
- Women of childbearing potential must have a negative serum beta-hCG or urine pregnancy test at Screening.
- Sign of an informed consent document.The informed consent document can be signed by a person of confidence in case neurologic disorders related to the disease prevent the patient to sign himself.
Exclusion Criteria:
- Contraindication to any excipients of the drug.
- T-cell lymphoma.
- Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast), prior history of systemic lymphoma, unless the patient has been free of the disease for ≥ 3 years.
- Prior history of organ transplantation or other cause of severe immunodeficiency.
- Major surgery, within 4 weeks prior to the first dose of study drug.
- History of stroke or intracranial hemorrhage within 6 months prior to randomization. Patients with post-biopsies hemorrhagic sequela defined as a small hyperdense lesion < 3 mm on T2* sequence won't be excluded.
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists or ongoing warfarin medication or other equivalent vitamin K antagonists.
- Any anti-platelet aggregant medication except acetyl salicylic acid ≤ 75 mg/day.
- Requires treatment with strong CYP3A4 inhibitors.
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 or Class 4 cardiac disease as defined by the New York Heart Association Functional Classification.
- Vaccinated with live, attenuated vaccines within 4 weeks prior to the first dose of study drug.
- Known history of HIV or active Hepatitis C Virus (HCV; RNA polymerase chain reaction [PCR]-positive) or active Hepatitis B Virus (HBs Ag positive or DNA PCR-positive) infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics.
- Any life-threatening illness, medical condition, or organ system dysfunction which could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.
- Inability to swallow capsules.
- Pregnancy or lactation.
- Use of anti-cancer drug therapy within 21 days prior to the first dose of study drug.
- Previous treatment by BTK inhibitors and PI3K inhibitors.
- Known bleeding diathesis.
- Inclusion in another experimental anti-cancer drug therapy*.
- Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
- Patient under measure of legal protection.
- No social security affiliation.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Ibrutinib
ibrutinib in monotherapy 28 days/cycles
|
p.o. 560 mg once a day (four 140 mg capsules) for one year (12 cycles of 28 days)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
disease control rate (CR + CRu + PR +SD)
Time Frame: 2 months
|
Disease control (DC) rate (CR + CRu + PR + SD) after 2 cycles of treatment according to IPCG criteria.
|
2 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
progression-free survival (PFS)
Time Frame: 12 months
|
12 months
|
|
time to progression
Time Frame: 12 months
|
12 months
|
|
Number of AE
Time Frame: 12 months
|
To evaluate tolerance and toxicity of ibrutinib.
|
12 months
|
disease control
Time Frame: 4, 6, 9 and 12 months
|
according to IPCG criteria evaluated locally by investigators and the results of the MRI review (maximum of 6 MRI review per patient).
|
4, 6, 9 and 12 months
|
overall response (OR)
Time Frame: 4, 6, 9 and 12 months
|
according to IPCG criteria evaluated locally by investigators and the results of the MRI review (maximum of 6 MRI review per patient).
|
4, 6, 9 and 12 months
|
complete response (CR) rate
Time Frame: 4, 6, 9 and 12 months
|
according to IPCG criteria evaluated locally by investigators and the results of the MRI review (maximum of 6 MRI review per patient).
|
4, 6, 9 and 12 months
|
overall survival (OS)
Time Frame: 4, 6, 9 and 12 months
|
according to IPCG criteria evaluated locally by investigators and the results of the MRI review (maximum of 6 MRI review per patient).
|
4, 6, 9 and 12 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
concentration of ibrutinib in cerebrospinal fluid
Time Frame: baseline and 2 months
|
Pharmacokinetics of ibritunib in the cerebrospinal fluid.
|
baseline and 2 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Chair: Carole Soussain, MD, Lymphoma Study Association
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
September 1, 2015
Primary Completion (ACTUAL)
August 1, 2016
Study Completion (ACTUAL)
December 1, 2021
Study Registration Dates
First Submitted
August 31, 2015
First Submitted That Met QC Criteria
September 4, 2015
First Posted (ESTIMATE)
September 7, 2015
Study Record Updates
Last Update Posted (ACTUAL)
April 14, 2022
Last Update Submitted That Met QC Criteria
April 6, 2022
Last Verified
April 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- iLOC
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Intraocular Lymphoma
-
Peking Union Medical College HospitalRecruitingPrimary Intraocular LymphomaChina
-
University of California, San FranciscoCompletedIntraocular Lymphoma | Central Nervous System LymphomaUnited States
-
James RubensteinGenentech, Inc.; CelgeneCompletedIntraocular Lymphoma | Recurrent/Refractory CNSUnited States
-
Peking Union Medical College HospitalBeijing Tongren Hospital; Southern Medical UniversityRecruitingPrimary Vitreoretinal LymphomaChina
-
Peking Union Medical College HospitalRecruiting
-
Vinodh Kakkassery, MDUniversity Hospital Tuebingen; University Hospital Schleswig-HolsteinNot yet recruiting
-
Mayo ClinicNational Cancer Institute (NCI)CompletedRecurrent Adult Diffuse Large Cell Lymphoma | Intraocular Lymphoma | Central Nervous System Lymphoma | B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma | Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System and other conditionsUnited States
-
National Taiwan University HospitalNot yet recruitingPrimary Central Nervous System Lymphoma and Primary Vitreoretinal Lymphoma
-
Sun Yat-sen UniversityEnrolling by invitation
-
University of PittsburghRecruiting
Clinical Trials on Ibrutinib
-
Christian BuskeAmgen; Janssen, LPRecruitingWaldenstrom MacroglobulinemiaAustria, Germany, Greece
-
TG Therapeutics, Inc.CompletedMantle Cell Lymphoma | Chronic Lymphocytic LeukemiaUnited States
-
Johnson & Johnson Private LimitedCompletedLymphoma, Mantle-Cell | Leukemia, Lymphocytic, Chronic, B-CellIndia
-
Janssen Research & Development, LLCCompleted
-
Janssen Research & Development, LLCCompleted
-
Oncternal Therapeutics, IncUniversity of California, San Diego; Pharmacyclics LLC.; California Institute...Active, not recruitingMantle Cell Lymphoma | Marginal Zone Lymphoma | B-cell Chronic Lymphocytic Leukemia | Small Lymphocytic LymphomaUnited States
-
The Lymphoma Academic Research OrganisationJanssen Pharmaceutica N.V., BelgiumTerminatedB-cell LymphomaFrance, Belgium
-
Pharmacyclics Switzerland GmbHJanssen Biotech, Inc., including Johnson & JohnsonEnrolling by invitationLymphoma, B-Cell | Lymphoma, Non-Hodgkin | Solid Tumor | Leukemia, B-cell | Graft Vs Host DiseaseUnited States, Spain, Taiwan, United Kingdom, Australia, Italy, Russian Federation, Canada, New Zealand, Korea, Republic of, France, Turkey, Czechia, Hungary, Poland, Sweden
-
Janssen-Cilag Ltd.CompletedLymphoma, Mantle-Cell | Leukemia, Lymphocytic, Chronic, B-CellFrance
-
Gruppo Italiano Malattie EMatologiche dell'AdultoCompletedChronic Lymphocytic LeukemiaItaly