a Phase II Study in Primary Central Nervous System Lymphoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2007 by National Health Research Institutes, Taiwan.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
National Taiwan University Hospital
Mackay Memorial Hospital
China Medical University Hospital
National Cheng-Kung University Hospital
Chi Mei Medical Hospital
Taichung Veterans General Hospital
Information provided by:
National Health Research Institutes, Taiwan
ClinicalTrials.gov Identifier:
NCT00455286
First received: April 2, 2007
Last updated: April 3, 2007
Last verified: April 2007
  Purpose

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

Condition Intervention Phase
Primary Central Nervous System Lymphoma
Drug: Methotrexate
Drug: Methylprednisolone
Drug: Temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High-Dose Methotrexate Plus Steroid Followed by Concurrent Whole Brain Chemoradiation With Temozolomide for Immunocompetent Patients With Primary Central Nervous System Lymphoma – a Phase II Study

Resource links provided by NLM:


Further study details as provided by National Health Research Institutes, Taiwan:

Primary Outcome Measures:
  • Primary : To evaluate objective tumor response rate


Secondary Outcome Measures:
  • Secondary : To assess toxicity profile
  • To assess time to disease progression

Estimated Enrollment: 25
Study Start Date: November 2006
Estimated Study Completion Date: November 2011
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients must fulfill all the following criteria to be eligible for admission for the study:

  1. Histologically proven central nervous system lymphoma of brain parenchyma with or without leptomeningeal involvement.
  2. No evidence of systemic lymphoma.
  3. Age between 18 years and 75 years.
  4. With at least one measurable lesion, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 10 mm. See Section 10.2.1 for the evaluation of measurable disease.
  5. Laboratory requirements :

    • Hematology: Neutrophils≧ 1500/mm3, Hemoglobin≧ 10 g/dL, and Platelet count≧ 100000/mm3.
    • Hepatic function: Total bilirubin level≦ 1.5x upper normal limit (UNL), ALT (SGPT) and AST (SGOT)≦ 2.5 x UNL.
    • Renal function: Creatinine≦ 1.5 mg/dL.
  6. No prior malignancy (excluding in situ carcinoma of the cervix or non- melanomatous skin cancer) unless disease free for at least 5 years.
  7. Signed informed consent.
  8. Patients must be accessible for treatment and follow-up.

Exclusion Criteria:

Patient meets any of the following will be excluded form the study.

  1. Patients who are seropositive for HIV, AIDS, use of immunosuppressant or who are post organ transplant are not eligible.
  2. Previously treated with chemotherapy, radiotherapy or other investigational agents. Patients with corticosteroid use are considered eligible.
  3. With ocular involvement or with any lesion beyond brain parenchyma except leptomeningeal.
  4. Pregnant, or lactating patients; patients of childbearing potential must implement adequate contractive measures during study participation.
  5. Other serious illness or medical conditions:

    • Congestive heart failure or unstable angina pectoris. High risk uncontrolled arrhythmias.
    • Uncontrolled infection (active serous infections that are not controlled by antibiotics.
  6. Concurrent treatment with any other experimental drugs.

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  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00455286

Contacts
Contact: Yueh-Ling Ho, RN 886-2-87923311 ext 17642 ylho@nhri.org.tw
Contact: Ching-Hung Lin, M.D. 886-2-2312-3456 ext 2859 dtmed004@ha.mc.ntu.edu.tw

Locations
Taiwan
Changhua Christian Hospital Recruiting
Changhua, Taiwan
Contact: Cheng-Shyong Chang, M.D.    886-4-7238595    15120@cch.org.tw   
China Medical University Hospital Recruiting
Taichung, Taiwan
Contact: Chang-Fang Chiu Chiu, M.D.    886-4-22052121    d5686@www.cmuh.org.tw   
National Cheng Kung University Hospital Recruiting
TaiNan, Taiwan
Contact: Wu-Chou Su, M.D.    886-6-2353535    sunnysu@mail.ncku.edu.tw   
Mackay Memorial Hospital Recruiting
Taipei, Taiwan
Contact: Ming-Chih Chang, M.D.    886-2-25433535 ext 3454    mmhdonald@yahoo.com.tw   
Contact: Ming-Jer Huang         
Sponsors and Collaborators
National Health Research Institutes, Taiwan
National Taiwan University Hospital
Mackay Memorial Hospital
China Medical University Hospital
National Cheng-Kung University Hospital
Chi Mei Medical Hospital
Taichung Veterans General Hospital
Investigators
Principal Investigator: Ching-Hung Lin, M.D. National Taiwan University Hospital
Study Chair: Ann-Lii Cheng, Ph.D. National Taiwan University Hospital
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00455286     History of Changes
Other Study ID Numbers: T1406
Study First Received: April 2, 2007
Last Updated: April 3, 2007
Health Authority: Taiwan: Department of Health

Keywords provided by National Health Research Institutes, Taiwan:
CNS Lymphoma

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Methotrexate
Temozolomide
Methylprednisolone Hemisuccinate
Prednisolone
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents

ClinicalTrials.gov processed this record on April 15, 2014