Methotrexate, Glucarpidase, and Leucovorin in Treating Patients With Newly Diagnosed Primary Central Nervous System Lymphoma

NCT ID: NCT00727831

Last Updated: 2014-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2011-07-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as methotrexate and leucovorin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Glucarpidase may help return the level of methotrexate in the blood to a safe range. Giving high-dose methotrexate together with glucarpidase and leucovorin may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of methotrexate when given together with glucarpidase and leucovorin in treating patients with newly diagnosed primary central nervous system lymphoma.

Detailed Description

OBJECTIVES:

Primary

• To determine the dose-limiting toxicity of methotrexate (MTX) when given in combination with glucarpidase in patients with newly diagnosed primary CNS lymphoma (PCNSL).
• To determine the incidence of immediate reactions related to the use of glucarpidase in these patients.
• To define a safer, more practical, and simpler regimen for delivering multiple courses of high-dose MTX using glucarpidase and 'short' leucovorin calcium rescue in these patients.
• To monitor quality of life and mental function during and after therapy in these patients.

Secondary

• To use this regimen as a platform for phase III studies in PCNSL.
• To record disease response, duration of response, and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of high-dose methotrexate (HD-MTX).

Patients receive HD-MTX IV over 4 hours on day 1. Beginning 22 hours after the start of HD-MTX, patients receive glucarpidase IV over 15 minutes on day 2 followed by leucovorin calcium orally or IV on days 2-7. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Within 2-4 weeks after completion of study treatment, patients achieving maximum response are stratified according to age (< 60 years vs ≥ 60 years) and may undergo whole brain radiotherapy (WBRT) once daily, 5 days a week, for 3 to 5 weeks.

Patients undergo blood sample collection periodically to assess glucarpidase antibodies and MTX levels.

Patients are assessed for mucositis incidence and severity periodically, and complete quality of life assessments using the EORTC QLQ-30 questionnaire and the Mini-Mental State questionnaire at baseline, during, and after completion of study.

After completion of study treatment, patients are followed at 6 weeks after WBRT, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

Conditions

Chemotherapeutic Agent Toxicity; Lymphoma; Mucositis; Neurotoxicity

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

glucarpidase

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

quality-of-life assessment

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• No clinically significant effusions or edema

PATIENT CHARACTERISTICS:

• ECOG performance status 0-3
• Neutrophils ≥ 1 x 10^9/L
• Platelet count ≥ 100 x 10^9/L
• Bilirubin < 1.5 times upper limit of normal
• Glomerular filtration rate (initially measured by EDTA/isotope method) ≥ 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after completion of study therapy

Exclusion Criteria

• HIV positivity
• Dementia or neurological dysfunction not considered to be due to the PCNSL
• Other serious or uncontrolled medical conditions
• Prior malignancy, except adequately treated nonmelanoma skin cancer or carcinoma in situ

PRIOR CONCURRENT THERAPY:

• No prior cytotoxic chemotherapy
• No concurrent prophylactic antibiotics
• No concurrent co-trimoxazole

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Research UK

OTHER

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roderick Johnson, MD

Role: PRINCIPAL_INVESTIGATOR

Leeds General Infirmary

Locations

Leeds General Infirmary

Leeds, England, United Kingdom

Torbay Hospital

Torquay, England, United Kingdom

Countries

United Kingdom

Other Identifiers

CRUK-BRD/07/004

Identifier Type: -

Identifier Source: secondary_id

2007-002570-58

Identifier Type: -

Identifier Source: secondary_id

EU-20861

Identifier Type: -

Identifier Source: secondary_id

CDR0000599206

Identifier Type: -

Identifier Source: org_study_id