Methotrexate and Thiotepa in Treating Patients With Newly Diagnosed Primary CNS Lymphoma

Lymphoma Clinical Trial

Official title:

A Phase II Study of Methotrexate and Thiotepa Chemotherapy for Patients With Newly Diagnosed Primary CNS Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00045539
• Other study ID #: CDR0000256605
• Secondary ID: NABTT-2109JHOC-N
• Status: Completed
• Phase: Phase 2
• First received: September 6, 2002
• Last updated: June 21, 2013
• Start date: October 2002
• Est. completion date: January 2006

Study information

• Verified date: December 2005
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as methotrexate and thiotepa, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining methotrexate with thiotepa in treating patients who have newly-diagnosed primary CNS lymphoma.

Description:

OBJECTIVES:

• Determine the complete radiographic response in patients with newly diagnosed primary CNS lymphoma treated with methotrexate and thiotepa.

• Determine the duration of progression-free survival and overall survival of patients treated with this regimen.

• Determine the toxicity of this regimen in these patients.

• Determine whether tumor expression of BCL-6 is associated with response to this chemotherapy regimen and survival of these patients.

• Describe the relationship between initial response to steroids (if administered), response to this chemotherapy regimen, and survival of these patients.

OUTLINE: This is a multicenter study.

Patients receive thiotepa IV over 15 minutes on day 1. Patients also receive methotrexate IV over 4 hours on days 1 (8 hours after thiotepa) and 14. Beginning 24 hours after the start of methotrexate infusion, patients receive leucovorin calcium IV or orally every 6 hours until rescue is achieved. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving disappearance of enhancement of disease on MRI receive an additional 28-day course followed by maintenance therapy comprising thiotepa and methotrexate once a month for 11 courses.

Patients undergo neuro-ophthalmologic exams annually for 2 years.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 23-39 patients will be accrued for this study within 8-20 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed primary CNS lymphoma

• Confirmed by 1 of the following:

• Brain biopsy or resection

• CSF cytology

• Positive cytology or immunohistochemical diagnosis of monoclonality and measurable intracranial tumor

• Vitreal biopsy

• Measurable and contrast-enhancing disease on the postoperative, pretreatment MRI or CT scan

• No radiographic evidence of ascites or pleural effusions

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 2.0 mg/dL

• SGOT no greater than 4 times upper limit of normal

Renal

• Creatinine no greater than 2 mg/dL

• Creatinine clearance at least 50 mL/min

Other

• Mini mental score of at least 15

• HIV negative

• Able to achieve hydration

• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ

• No allergy to methotrexate

• No serious infection

• No medical illness that would preclude study participation

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy or biologic therapy for this disease

Chemotherapy

• No prior chemotherapy for this disease

• No other concurrent chemotherapeutic agents

Endocrine therapy

• No prior hormonal therapy for this disease

• Prior glucocorticoid therapy allowed

Radiotherapy

• No prior radiotherapy for this disease

• No prior cranial irradiation

Surgery

• See Disease Characteristics

Other

• At least 1 week since prior salicylates, non-steroidal anti-inflammatory drugs, probenecid, folic acid, or sulfonamide medications

• No other concurrent investigational agents

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma

Intervention

Drug:
• leucovorin calcium

• methotrexate

• thiotepa

Locations

Country	Name	City	State
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
New Approaches to Brain Tumor Therapy Consortium	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete radiographic response			No
Secondary	Duration of progression-free survival and overall survival			No
Secondary	Toxicity			Yes
Secondary	Association of tumor BCL-6 expression with response			No
Secondary	Relationship among initial response to steroids, response to chemotherapy, and survival			No