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.
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
Drug | Synonyms | Arms |
---|
IBER salvage chemotherapy followed by ibrutinib maintenance therapy | | IBER 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
Name | Type | Description | Interventions |
---|
IBER treatment arm | Experimental | This 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 |
Last Updated
August 26, 2019