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

August 22, 2019 updated by: Deok-Hwan Yang

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Yoon Seok Choi, M.D., Ph.D.
  • Phone Number: +82-42-280-7107
  • Email: wyfran@gmail.com

Study Locations

  • Korea, Republic of
    • Jeollanam-do
      • Hwasun, Jeollanam-do, Korea, Republic of, 519-809
        • Chonnam National University Hwasun Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IBER treatment arm
This is the only arm in a single-arm phase II study.
Drug: IBER salvage chemotherapy followed by ibrutinib maintenance therapy
Induction therapy with IBER (up to 6 cycles) [ Ibrutinib 560 mg/d on D1-21 + Rituximab 375 mg/m2 on D1 (on D1/8/15 in C1) + Ifosfamide 3.75 g/m2 on D2 + Etoposide 100 mg/m2 on D2-4 ], followed by ibrutinib 560 mg/d maintenance therapy for up to 6 months

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Treatment-emergent adverse events graded according to the NCI-CTCAC version 4.0
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Deok-Hwan Yang

Investigators

  • Principal Investigator: Deok-Hwan Yang, Chonnam National University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

October 1, 2019

Primary Completion (Anticipated)

September 30, 2021

Study Completion (Anticipated)

September 30, 2023

Study Registration Dates

First Submitted

August 20, 2019

First Submitted That Met QC Criteria

August 22, 2019

First Posted (Actual)

August 26, 2019

Study Record Updates

Last Update Posted (Actual)

August 26, 2019

Last Update Submitted That Met QC Criteria

August 22, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IBER

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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