Phase I Trial of Escalating High Dose Methotrexate Supported by Glucarpidase to Treat Patients With Primary Central Nervous Lymphoma (PCNSL)
18 Years
N/A
Both
Chemotherapeutic Agent Toxicity, Lymphoma, Mucositis, Neurotoxicity
Trial Information
Phase I Trial of Escalating High Dose Methotrexate Supported by Glucarpidase to Treat Patients With Primary Central Nervous Lymphoma (PCNSL)
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed newly diagnosed primary CNS lymphoma (PCNSL)
- Previously untreated disease
- Diffuse large B-cell lymphoma histology
- Must be clinically eligible to receive standard 3 g/m² methotrexate if outside trial
- No clinically significant effusions or edema
PATIENT CHARACTERISTICS:
Inclusion criteria:
- 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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Immediate toxicity (incidence of reactions to glucarpidase) as determined by the NCI CTC
Safety Issue:
Yes
Principal Investigator
Roderick Johnson, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Leeds General Infirmary
Authority:
Unspecified
Study ID:
CDR0000599206
NCT ID:
NCT00727831
Start Date:
July 2008
Completion Date:
Related Keywords:
- Chemotherapeutic Agent Toxicity
- Lymphoma
- Mucositis
- Neurotoxicity
- 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
- Lymphoma
- Neurotoxicity Syndromes
- Mucositis
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