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

NCT ID: NCT02623010

Last Updated: 2022-05-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2023-12-31

Brief Summary

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

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

Conditions

Central Nervous System Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Imbruvica

Intervention Type: DRUG

Bruton's Tyrosine Kinase Inhibitor Ibrutinib as maintenance treatment in elderly patients with primary CNS lymphoma following first line chemotherapy treatment

Interventions

Imbruvica

Bruton's Tyrosine Kinase Inhibitor Ibrutinib as maintenance treatment in elderly patients with primary CNS lymphoma following first line chemotherapy treatment

Intervention Type: DRUG

Other Intervention Names

Ibrutinib; JNJ-54179060

Eligibility Criteria

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.

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen, LP

INDUSTRY

Sponsor Role: collaborator

Rabin Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Osnat Bairey

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Osnat Bairey, MD

Role: PRINCIPAL_INVESTIGATOR

Senior Hematologist, Rabin Medical Center

Locations

Hematology Institute

Petah Tikva, , Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

Osnat Bairey, MD

Role: CONTACT

osnatb@clalit.org.il

972504065471

Tali Siegal, MD

Role: CONTACT

talisi1@clalit.org.il

97239377950

Facility Contacts

Osnat Bairey, MD

Role: primary

osnatb@clalit.org.il

972504065471

Tali Siegal, MD

Role: backup

talisi1@clalit.org.il

97239377950

References

Bairey O, Taliansky A, Glik A, Amiel A, Yust-Katz S, Gurion R, Zektser M, Porges T, Sarid N, Horowitz NA, Shina TT, Lebel E, Cohen A, Geiger KR, Raanani P, Wolach O, Siegal T. A phase 2 study of ibrutinib maintenance following first-line high-dose methotrexate-based chemotherapy for elderly patients with primary central nervous system lymphoma. Cancer. 2023 Dec 15;129(24):3905-3914. doi: 10.1002/cncr.34985. Epub 2023 Aug 12.

Reference Type: DERIVED

PMID: 37572086 (View on PubMed)

Other Identifiers

0356-15-RMC

Identifier Type: -

Identifier Source: org_study_id