Clinical Trial: Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Patients With Refractory/Recurrent Primary Central Nervous System Lymphoma (PCNSL) and Refractory/Recurrent Secondary Central Nervous System Lymphoma (SCNSL)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase I/II Trial of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Patients With Refractory/Recurrent Primary Central Nervous System Lymphoma (PCNSL) and Re

Brief Summary: The purpose of this study is to test any good or bad effects of the study drug called of ibrutinib (also known as Imbruvica™) at 840mg daily dosing has on the patient and the lymphoma in the central nervous system.

Detailed Summary:
Sponsor: Memorial Sloan Kettering Cancer Center

Current Primary Outcome:

  • define the Maximum Tolerated Dose (MTD) of ibrutinib (phase I) [ Time Frame: 1 year ]
    A standard 3+3 design will be employed. Three dose levels of ibrutinib will be investigated. Patients will be treated in cohorts of size three to six and the dosage will be escalated if the clinical toxicity is acceptable. A dose-limiting toxicity (DLT) is defined as in any of the following during cycle 1: any grade 4 hematologic toxicity, grade 3 febrile neutropenia and grade 3 thrombocytopenia associated with bleeding or any grade 3 non-hematologic toxicity that does not respond to supportive therapy and at least possibly related to treatment with ibrutinib.
  • progression free survival (phase II) [ Time Frame: 2 years ]
    Progression-free survival (PFS) is defined as the time from the date of treatment start to the date of the first documented PD or death due to any cause.
  • define the Maximum Tolerated Dose (MTD) of ibrutinib in combination with high-dose Methotrexate (HD-MTX) [ Time Frame: 1 year ]
    Three patients with PCNSL or SCNSL will be treated with daily oral ibrutinib +/- HD-MTX for a 28-day cycle starting at dose level 1 and observed for toxicities for a minimum of 4 weeks. Dose-limiting toxicity (DLT) will be defined as any grade 4 hematologic toxicity, grade 3 febrile neutropenia and grade 3 thrombocytopenia associated with bleeding as well as any grade 3 non-hematologic toxicity that does not respond to supportive therapy and at least possibly related to ibrutinib. If no DLT is observed in any of the 3 treated patients, we will escalate to the next dose level.


Original Primary Outcome:

  • define the Maximum Tolerated Dose (MTD) of ibrutinib (phase I) [ Time Frame: 1 year ]
    A standard 3+3 design will be employed. Four dose levels of ibrutinib will be investigated. Patients will be treated in cohorts of size three to six and the dosage will be escalated if the clinical toxicity is acceptable. A dose-limiting toxicity (DLT) is defined as in any of the following during cycle 1: any grade 4 hematologic toxicity, grade 3 febrile neutropenia and grade 3 thrombocytopenia associated with bleeding or any grade 3 non-hematologic toxicity that does not respond to supportive therapy and at least possibly related to treatment with ibrutinib.
  • progression free survival (phase II) [ Time Frame: 2 years ]
    Progression-free survival (PFS) is defined as the time from the date of treatment start to the date of the first documented PD or death due to any cause.


Current Secondary Outcome:

  • safety/tolerability of ibrutinib in patients by assessing the frequency and severity of adverse events [ Time Frame: 1 year ]

    in patients by assessing the frequency and severity of adverse events.

    1. The severity grade (CTCAE Grade 1-4)
    2. Its duration (Start and end dates)
    3. Its relationship to the study treatment (Reasonable possibility that AE is related: No, Yes)
    4. Action taken with respect to study or investigational treatment (none, dose adjusted, temporarily interrupted, permanently discontinued, unknown, ongoing, not applicable)
  • progression free survival [ Time Frame: 16 weeks, 24 weeks & 48 weeks ]
    Progression-free survival (PFS) is defined as the time from the date of treatment start to the date of the first documented PD or death due to any cause.
  • Duration of response [ Time Frame: 2 years ]
    Duration of response is defined as the time from the date of first occurrence of CR or PR to the date of the first documented PD or death due to any cause.Duration of response will be described using Kaplan-Meier curves with appropriate summary statistics


Original Secondary Outcome: Same as current

Information By: Memorial Sloan Kettering Cancer Center

Dates:
Date Received: December 9, 2014
Date Started: December 2014
Date Completion: December 2018
Last Updated: February 22, 2017
Last Verified: February 2017