Clinical Trials /

IBER Salvage Treatment Followed by Ibrutinib Maintenance for Relapsed or Refractory PCNSL

NCT04066920

Description:

This is a multicenter, single-arm, prospective phase II study to evaluate the efficacy and safety of a novel combination regimen for relapsed/refractory PCNSL. Specifically, ibrutinib will be administered in combination with ifosfamide, etoposide and rituximab (IBER) as a salvage chemotherapy, which is followed by maintenance ibrutinib monotherapy of fixed duration.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Primary Central Nervous System Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: IBER Salvage Treatment Followed by Ibrutinib Maintenance for Relapsed or Refractory PCNSL
  • Official Title: Clinical Efficacy and Safety of IBER Salvage Treatment Followed by Ibrutinib Maintenance for Transplant-ineligible Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma (PCNSL): a Multicenter, Single-arm, Prospective Phase II Study

Clinical Trial IDs

  • ORG STUDY ID: IBER
  • NCT ID: NCT04066920

Conditions

  • Primary Central Nervous System Lymphoma

Interventions

DrugSynonymsArms
IBER salvage chemotherapy followed by ibrutinib maintenance therapyIBER treatment arm

Purpose

This is a multicenter, single-arm, prospective phase II study to evaluate the efficacy and safety of a novel combination regimen for relapsed/refractory PCNSL. Specifically, ibrutinib will be administered in combination with ifosfamide, etoposide and rituximab (IBER) as a salvage chemotherapy, which is followed by maintenance ibrutinib monotherapy of fixed duration.

Detailed Description

      Given the limited activity of salvage therapy with high-dose methotrexate re-treatment and/or
      alkylator-based treatment in patients with relapse or refractory PCNSL, the development of
      novel salvage chemotherapy regimen remains an area of clinical unmet need.

      Ibrutinib, an oral inhibitor of bruton tyrosine kinase (BTK), is known to induce death of
      diffuse large B-cell lymphoma (DLBCL) cells with dysregulated B-cell receptor (BCR) signaling
      and has shown promising activity in patients with a variety of B-cell malignancies. Recently,
      several studies reported that ibrutinib may have an excellent single-agent clinical activity
      against relapsed or refractory PCNSL. Furthermore, proven pharmacokinetic data suggested that
      ibrutinib successfully penetrated the BBB and reached the achievable concentration in
      cerebrospinal fluid. When ibrutinib is administered in combination with BBB-destructing
      chemotherapeutic agents (such as, temozolomide or etoposide) for salvage treatment of PCNSL,
      therefore, anti-lymphoma activity of ibrutinib could be maximized.

      In this context, this phase II study is designed to evaluate the efficacy and safety of IBER
      salvage chemotherapy followed by ibrutinib maintenance for transplant ineligible patients
      with relapsed or refractory PCNSL.
    

Trial Arms

NameTypeDescriptionInterventions
IBER treatment armExperimentalThis is the only arm in a single-arm phase II study.
  • IBER salvage chemotherapy followed by ibrutinib maintenance therapy

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed PCNSL of CD20+ diffuse large B cell lymphoma (DLBCL)

          -  PCNSL relapsed or refractory after frontline methotrexate-based chemotherapy (with or
             without radiation therapy)

          -  At least one measurable lesion, which is defined as longest diameter of lesion > 0.5
             cm, by contrast-enhanced MRI

          -  ECOG performance status 0-2

          -  Normal function of major organs

        Exclusion Criteria:

          -  PCNSL other than DLBCL

          -  Primary ocular lymphoma

          -  PCNSL accompanied by systemic involvement

          -  Active infection with hepatitis B or C virus

          -  Known history of human immunodeficiency virus (HIV) infection

          -  Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to
             registration
      
Maximum Eligible Age:79 Years
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate
Time Frame:From date of starting the study treatment until the date of finishing the study treatment for any reason, assessed up to 10 months
Safety Issue:
Description:The percentage of patients with a complete response (CR) or a partial response (PR)

Secondary Outcome Measures

Measure:Safety and tolerability of the study treatment
Time Frame:From the first day of the first cycle of IBER induction chemotherapy to 30 days after the last dose of study drug, assessed up to 12 months
Safety Issue:
Description:Treatment-emergent adverse events graded according to the NCI-CTCAC version 4.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Deok-Hwan Yang

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