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

NCT00727831 | Completed Phase 1 DMC

• 4 other identifiers: CDR0000599206CRUK-BRD/07/0042007-002570-58EU-20861
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

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.

Conditions

Chemotherapeutic Agent Toxicity; Lymphoma; Mucositis; Neurotoxicity

Keywords

neurotoxicity; chemotherapeutic agent toxicity; mucositis; primary central nervous system non-Hodgkin lymphoma; contiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; stage I adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma

Outcome Measures

Primary Outcomes (4)

• Immediate toxicity (incidence of reactions to glucarpidase) as determined by the NCI CTC

• Incidence and severity of renal dysfunction as determined by the NCI CTC

• Incidence and severity of mucositis as determined by the NCI CTC and WHO mucositis grading scale

• Incidence and severity of CNS toxicity and neurocognitive changes taken from patients' medical records and measured using the Mini-Mental State questionnaire and MRI data

Secondary Outcomes (8)

• Hematological toxicity (i.e., number of courses of therapy associated with neutrophils < 0.5 x 10e9/L or platelets < 50 x 10e9/L as measured by routine blood counts)

• Incidence of infection (i.e., number of days with fever ≥ 38 C° measured by clinical examination and days of intravenous antibiotics taken from patients' medical records)

• Number of inpatient days taken from patients' medical records

• Disease response and remission rates measured by serial MRI scanning (and eye examination and lumbar puncture if necessary)

• Disease outcome, time to progression, and overall survival at 2 years from start of therapy measured by clinical examination and serial MRI scanning

Interventions

glucarpidase DRUG

leucovorin calcium DRUG

methotrexate DRUG

laboratory biomarker analysis OTHER

quality-of-life assessment PROCEDURE

radiation therapy RADIATION

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University College, London: lead
• Cancer Research UK: collaborator

Study Sites (2)

Leeds General Infirmary

Leeds, England, LS1 3EX, United Kingdom

Location

Torbay Hospital

Torquay, England, TQ2 7AA, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma; Mucositis; Neurotoxicity Syndromes; Lymphoma, Large B-Cell, Diffuse

Interventions

glucarpidase; Leucovorin; Methotrexate; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases; Nervous System Diseases; Poisoning; Chemically-Induced Disorders; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Aminopterin; Therapeutics

Study Officials

• Roderick Johnson, MD

  Leeds General Infirmary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2008
• First Posted: August 4, 2008
• Study Start: July 1, 2008
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: January 27, 2014

Record last verified: 2014-01

Locations

GB (2)