a Phase II Study in Primary Central Nervous System Lymphoma

Summary

In this study we will test the hypothesis that concurrent chemoradiation (CCRT) with temozolomide after induction chemotherapy by conventional high-dose methotrexate (HD-MTX) plus dexamethasone may be an effective and well tolerated treatment for immunocompetent patients with PCSNL. Corticosteroid can effectively reduce brain edema and corticosteroid alone has resulted in complete or partial remission in about 40% patients with PCNSL. To enhance local disease control, CCRT with temozolomide will be used in the study. Temozolomide is a well-tolerated oral alkylating agent that is able to permeate the BBB. Concurrent temozolomide with WBRT has shown superior effect to WBRT alone for the treatment of metastatic brain tumors and glioblastoma multiforme. In addition, temozolomide has single-agent activity for PCNSL (21% CR in relapsed or refractory PCNSL in a phase II trial).

This is an open-label, non-randomized, multi-center phase II study. The primary end point of is the complete response rate. This study is a two-stage design for testing non-inferiority of the proposed treatment as compared to the approximately 80% response rate reported for conventional treatment. Assuming a non-inferiority margin of 20%, a sample size of 25 subjects, which provides an 80% power for establishment of non-inferiority. At the first stage, 15 subjects are to be enrolled. If equal to or more than 6 patients achieve complete response, the study would accrue additional 10 subjects. The treatment regimen is as follows.

Induction chemotherapy: MS regimen (repeated every 14 days, total 4 cycles)

* Methotrexate 3.5 g/m2 i.v. infusion 4 hours on day1
* Methylprednisolone 200 mg/m2/day i.v. infusion 30 minutes, on day1-4 Concurrent chemoradiotherapy (CCRT)
* Whole brain radiation therapy (WBRT) 2 Gy per fraction daily, 5 days per week Temozolomide 75 mg/m2/day orally daily, only on the days of WBRT

Conditions

• Primary Central Nervous System Lymphoma

Interventions

DRUG

Methotrexate

DRUG

Methylprednisolone

DRUG

Temozolomide

Sponsors & Collaborators

• National Taiwan University Hospital

  collaborator OTHER

• Mackay Memorial Hospital

  collaborator OTHER

• China Medical University Hospital

  collaborator OTHER

• National Cheng-Kung University Hospital

  collaborator OTHER

• Chi Mei Medical Hospital

  collaborator OTHER

• Taichung Veterans General Hospital

  collaborator OTHER

• National Health Research Institutes, Taiwan

  lead OTHER

Principal Investigators

• Ching-Hung Lin, M.D. · National Taiwan University Hospital

• Ann-Lii Cheng, Ph.D. · National Taiwan University Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2006-11-30

Completion

2011-11-30

Countries

• Taiwan

Study Locations