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

Deok-Hwan Yang

Status and phase: Unknown; Phase 2

Conditions: Primary Central Nervous System Lymphoma

Treatments: Drug: IBER salvage chemotherapy followed by ibrutinib maintenance therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT04066920

IBER

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 20 to 79 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

IBER treatment arm

Experimental group

Description:

This is the only arm in a single-arm phase II study.

Treatment:

Drug: IBER salvage chemotherapy followed by ibrutinib maintenance therapy