Bruton's Tyrosine Kinase Inhibitor Ibrutinib as Maintenance Treatment in Elderly Patients With Primary CNS Lymphoma

Phase 2 Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib as Maintenance Treatment in Elderly Patients With Primary CNS Lymphoma Following First Line Chemotherapy Treatment

The study will include 30 elderly patients age 60-85 with primary CNS DLBCL . Induction treatment will include Rituximab and high dose methotrexate protocol (containing at least methotrexate and one more chemotherapy agent).

Patients with MRI documented response CR or PR will enter the study protocol maintenance phase which will include continous treatment with Ibrutinib 560 mg day until relapse or disease progression or occurrence of limiting toxicities

Study Overview

• Status: Recruiting
• Conditions: Central Nervous System Lymphoma
• Intervention / Treatment: Drug: Imbruvica

Detailed Description

30 elderly patients age 60-85 with primary CNS DLBCL who will achieve response CR or PR will enter the study protocol maintenance phase.

Induction treatment will include Rituximab and high dose methotrexate protocol (containing at least methotrexate and one more chemotherapy agent).

Patients with MRI documented response CR or PR will enter the study protocol maintenance phase.

Maintenance: 28 day cycles of Ibrutinib 560 mg orally once daily until relapse or disease progression or occurrence of limiting toxicities

Evaluation of response:

Radiologic evaluation by MRI will be performed every 3 months. Neurologic status evaluation every 2 months Neurocognitive evaluation every 6 months

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Osnat Bairey, MD; Phone Number: 972504065471; Email: osnatb@clalit.org.il
• Study Contact Backup: Name: Tali Siegal, MD; Phone Number: 97239377950; Email: talisi1@clalit.org.il

Study Locations

• Israel
  • Petah Tikva, Israel, 494192
    • Recruiting
    • Hematology Institute
    • Contact: Osnat Bairey, MD; Phone Number: 972504065471; Email: osnatb@clalit.org.il
    • Contact: Tali Siegal, MD; Phone Number: 97239377950; Email: talisi1@clalit.org.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newly diagnosed PCNSL patients whose age is >60 years and achieved response (CR/PR) after first line immunochemotherapy treatment
• Tissue diagnosis is mandatory unless positive cerebrospinal fluid (CSF) cytology or vitrectomy are diagnostic with no evidence for systemic disease
• No contraindication for high dose methotrexate (HD-MTX) (adequate renal function)
• KPS > 40%, ECOG < 3
• Hematology values must be within the following limits:

Absolute neutrophil count (ANC) ≥ 1000/µl independent of growth factor support Platelets ≥100,000/µl or ≥50,000/µl if bone marrow involvement independent of transfusion support in either situation • Biochemical values within the following limits: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockroft Gault≥ 40 mL/min

-

Exclusion Criteria:

• Major surgery within 4 weeks of randomization.
• History of stroke or intracranial hemorrhage within 6 months prior to randomization.
• Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon).
• Requires treatment with strong CYP3A 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 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.
• Vaccinated with live, attenuated vaccines within 4 weeks of randomization.
• Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics.
• Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; Imbruvica (ibrutinib) will be given as maintenance treatment until relapse or toxicity to 30 elderly PCNSL patients after achieving response to first line treatment	Drug: Imbruvica; Bruton's Tyrosine Kinase Inhibitor Ibrutinib as maintenance treatment in elderly patients with primary CNS lymphoma following first line chemotherapy treatment; Other Names: JNJ-54179060; Ibrutinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS- progression free survival	Progression free survival	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival	4 years

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Collaborators: Janssen, LP
• Investigators: Principal Investigator: Osnat Bairey, MD, Senior Hematologist, Rabin Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: October 14, 2015
• First Submitted That Met QC Criteria: December 2, 2015
• First Posted (Estimate): December 7, 2015

Study Record Updates

• Last Update Posted (Actual): May 10, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Elderly; Ibrutinib; Maintenance; Primary CNS lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: 0356-15-RMC