Study of Ibrutinib in Patients With Relapsed or Refractory Primary Central Nervous Lymphoma or Intraocular Lymphoma

NCT02542514 | Completed Phase 2 DMC

• 1 other identifier: iLOC
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Primary Central Nervous Lymphoma; Intraocular Lymphoma

Keywords

PCNSL; IOL

Outcome Measures

Primary Outcomes (1)

• disease control rate (CR + CRu + PR +SD)

  Disease control (DC) rate (CR + CRu + PR + SD) after 2 cycles of treatment according to IPCG criteria.

  2 months

Secondary Outcomes (7)

• Number of AE

  12 months

• disease control

  4, 6, 9 and 12 months

• overall response (OR)

  4, 6, 9 and 12 months

• complete response (CR) rate

  4, 6, 9 and 12 months

• overall survival (OS)

  4, 6, 9 and 12 months

Other Outcomes (1)

• concentration of ibrutinib in cerebrospinal fluid

  baseline and 2 months

Study Arms (1)

Ibrutinib

EXPERIMENTAL

ibrutinib in monotherapy 28 days/cycles

Drug: Ibrutinib

Interventions

Ibrutinib DRUG

p.o. 560 mg once a day (four 140 mg capsules) for one year (12 cycles of 28 days)

Ibrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead

Study Sites (10)

CHU d'ESTAING

Clermont-Ferrand, France

Location

CHU de Grenoble

Grenoble, France

Location

CHRU de LILLE - Claude Huriez

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

CHU de la Pitié Salpêtrière

Paris, France

Location

CHU de la Timone

Paris, France

Location

CHU de Rennes

Rennes, France

Location

Centre Henri Becquerel

Rouen, France

Location

Hôpital René Huguenin Institut Curie

Saint-Cloud, France

Location

CHU Brabois

Vandœuvre-lès-Nancy, France

Location

Related Publications (1)

• Soussain C, Choquet S, Blonski M, Leclercq D, Houillier C, Rezai K, Bijou F, Houot R, Boyle E, Gressin R, Nicolas-Virelizier E, Barrie M, Molucon-Chabrot C, Lelez ML, Clavert A, Coisy S, Leruez S, Touitou V, Cassoux N, Daniau M, Ertault de la Bretonniere M, El Yamani A, Ghesquieres H, Hoang-Xuan K. Ibrutinib monotherapy for relapse or refractory primary CNS lymphoma and primary vitreoretinal lymphoma: Final analysis of the phase II 'proof-of-concept' iLOC study by the Lymphoma study association (LYSA) and the French oculo-cerebral lymphoma (LOC) network. Eur J Cancer. 2019 Aug;117:121-130. doi: 10.1016/j.ejca.2019.05.024. Epub 2019 Jul 3.

  PMID: 31279304 DERIVED

MeSH Terms

Conditions

Intraocular Lymphoma

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Eye Neoplasms; Neoplasms by Site; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Carole Soussain, MD

  Lymphoma Study Association

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2015
• First Posted: September 7, 2015
• Study Start: September 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: December 1, 2021
• Last Updated: April 14, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (10)