Pilot Study of MGd + High-dose MTX-Based Chemoimmunotherapy + RT for Newly Dx PCNSL

Northwestern University

Status and phase

Withdrawn

Early Phase 1

Conditions

Brain and Central Nervous System Tumors

Lymphoma

Neurotoxicity

Treatments

Drug: Procarbazine hydrochloride

Radiation: Radiation therapy

Drug: Vincristine sulfate

Drug: Cytarabine

Biological: Rituximab

Drug: Methotrexate

Drug: Motexafin gadolinium

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00734773

NU 05H7

STU00002443 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Radiation therapy uses high-energy x-rays to kill cancer cells. Motexafin gadolinium may make cancer cells more sensitive to radiation therapy and combination chemotherapy. Giving motexafin gadolinium together with chemotherapy, rituximab, and radiation therapy may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects of giving motexafin gadolinium together with combination chemotherapy, rituximab, and whole-brain radiation therapy and to see how well it works in treating patients with newly diagnosed primary central nervous system lymphoma.

Full description

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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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