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

Sponsor

Deok-Hwan Yang (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04066920

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Central Nervous System Lymphoma	Drug: IBER salvage chemotherapy followed by ibrutinib maintenance therapy	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Oct 1, 2019

Anticipated Primary Completion Date :

Sep 30, 2021

Anticipated Study Completion Date :

Sep 30, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall response rate [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)

Secondary Outcome Measures

Safety and tolerability of the study treatment [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 79 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chonnam National University Hwasun Hospital	Hwasun	Jeollanam-do	Korea, Republic of	519-809

Sponsors and Collaborators

Deok-Hwan Yang

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Deok-Hwan Yang, Professor, Chonnam National University Hospital

ClinicalTrials.gov Identifier:

NCT04066920

Other Study ID Numbers:

IBER

First Posted:

Aug 26, 2019

Last Update Posted:

Aug 26, 2019

Last Verified:

Aug 1, 2019

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Lymphoma

Study Results

No Results Posted as of Aug 26, 2019