A Pilot Study Incorporating Motexafin Gadolinium (MGd) Into High-dose Methotrexate (MTX)-Based Chemo-immunotherapy and Radiation for Patients With Newly Diagnosed Primary CNS Lymphoma
18 Years
N/A
Both
Brain and Central Nervous System Tumors, Lymphoma, Neurotoxicity
Trial Information
A Pilot Study Incorporating Motexafin Gadolinium (MGd) Into High-dose Methotrexate (MTX)-Based Chemo-immunotherapy and Radiation for Patients With Newly Diagnosed Primary CNS Lymphoma
OBJECTIVES:
Primary
- Determine the safety and efficacy of motexafin gadolinium (MGd) combined with high-dose
methotrexate-based chemotherapy and radiotherapy in patients with newly diagnosed
primary CNS lymphoma.
- Determine the toxicity of MGd and rituximab combined with high-dose methotrexate,
procarbazine hydrochloride, and vincristine (MPV) in these patients.
- Determine the toxicity of MGd in combination with whole-brain radiotherapy (WBRT) in
these patients.
- Determine the tumor-selective uptake of MGd.
Secondary
- Determine the overall response rate (complete remission [CR] and partial remission
[PR]) in patients treated with pre-radiotherapy and chemo-immunotherapy (R-MPV with
MGd).
- Determine the complete response rate in patients treated with this regimen.
- Determine the overall response rate (CR and PR) in patients who complete all MGd
combined with high-dose methotrexate-based chemotherapy and WBRT.
- Determine the event-free and overall survival at 1 year of patients treated with this
regimen.
- Determine the progression-free survival at 1 year of patients treated with this
regimen.
- Evaluate the neurotoxicity of R-MVP with MGd based on pre- and post-treatment
neuropsychologic testing.
OUTLINE:
- Tumor-selective imaging: Patients receive motexafin gadolinium (MGd) IV on days 1-2
beginning 1-2 weeks prior to induction therapy. They then undergo an MRI of the brain.
- Induction therapy: Patients receive methotrexate IV over 2-3 hours and vincristine IV
on day 1 and rituximab IV over 5 hours and MGd IV over 30-60 minutes on day 8. Patients
also receive oral procarbazine hydrochloride on days 1-7 of courses 1, 3, and 5.
Treatment repeats every 14 days for 5 courses in the absence of disease progression or
unacceptable toxicity. Patients with partial response receive an additional 2 courses
of induction therapy.
- Chemoradiotherapy: Beginning 4 weeks after completion of induction therapy, patients
undergo reduced-dose whole-brain radiotherapy for 6 weeks. Patients also receive MGd IV
over 30-60 minutes, beginning 2-5 hours prior to radiotherapy, for 10 days and then
every other day during radiotherapy.
- Consolidation therapy: After completion of chemoradiotherapy, patients receive
cytarabine IV over 3 hours on days 1-2. Treatment repeats every 30 days for 2 courses.
After completion of study therapy, patients are followed every 3 months for the first year,
every 3-4 months for the second year, every 4-6 months until the fifth year, and then
annually thereafter.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed primary CNS lymphoma (PCNSL) diagnosed by brain biopsy, CSF
cytology, or vitreal biopsy
- Newly diagnosed disease
- Patients who have an inconclusive biopsy or who are not candidates for biopsy
may be eligible provided they have a typical cranial MRI or CT scan (defined as
the presence of hypo-, iso- or hyperdense parenchymal contrast-enhancing,
usually homogeneously) mass lesion(s) and meet at least one of the following
criteria:
- Positive cerebrospinal fluid cytology for lymphoma or a monoclonal
lymphocyte population as defined by cell surface markers
- Biopsy of the vitreous or uvea demonstrating non-Hodgkin lymphoma
- Measurable (defined as reproducibly measurable disease in two perpendicular
dimensions on radiologic study) or evaluable disease
PATIENT CHARACTERISTICS:
- ECOG performance status 0-3
- Life expectancy ≥ 8 weeks
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin ≤ 2.0 mg
- SGOT ≤ 2 times upper limit of normal
- Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance > 50 cc/min
- Not pregnant or nursing
- Fertile patients must use effective contraception during and for 6 months after
completion of study therapy
- HIV negative
- No other active primary malignancy with the exception of basal cell carcinoma of the
skin or cervical carcinoma in situ
PRIOR CONCURRENT THERAPY:
- No prior cranial irradiation
- No prior chemotherapy for CNS lymphoma
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Toxicity of motexafin gadolinium (MGd) and rituximab added to high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) chemotherapy
Outcome Description:
To evaluate toxicity of motexafin gadolinium (MGd) and rituximab to high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) chemotherapy at Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.
Outcome Time Frame:
Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.
Safety Issue:
Yes
Principal Investigator
Andrew M. Evens, DO, MS
Investigator Role:
Principal Investigator
Investigator Affiliation:
Robert H. Lurie Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NU 05H7
NCT ID:
NCT00734773
Start Date:
November 2008
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- Lymphoma
- Neurotoxicity
- neurotoxicity
- primary central nervous system non-Hodgkin lymphoma
- primary central nervous system Hodgkin lymphoma
- Lymphoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Neurotoxicity Syndromes
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