Neoplasms

Blood and Lymph Conditions

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Lymphoma

Neoplasms by Histologic Type

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Immunoproliferative Disorders

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Primary Central Nervous System Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

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Amino Acids

Etoposide

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Ibrutinib

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Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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

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

IBER salvage chemotherapy followed by ibrutinib maintenance therapy

Deok-Hwan Yang, M.D., Ph.D.

Yoon Seok Choi, M.D., Ph.D.

Deok-Hwan Yang

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.

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.

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

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

The percentage of patients with a complete response (CR) or a partial response (PR)

Treatment-emergent adverse events graded according to the NCI-CTCAC version 4.0

Professor

Spots Global Cancer Trial Database for iber salvage chemotherapy followed by ibrutinib maintenance therapy