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

Summary

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.

Conditions

• Brain and Central Nervous System Tumors
• Lymphoma
• Neurotoxicity

Interventions

BIOLOGICAL

Rituximab

Infusion will be given at week 2, week 4, week 6 and week 8. Infusions can be administered at an initial rate of 100 mg/hr, and increased by 100 mg/hr increments at 30-minute intervals, to a maximum of 400 mg/hr as tolerated.

DRUG

Cytarabine

Administered by IV over 3 hours at a dose of 3 g/m2/day for 2 days given at week 17 and week 21.

DRUG

Methotrexate

Administered by IV at dose of 3.5 grams/m2 on day 1 of week 1, week 3, week 5, week 7 and week 9; if CSF was positive it will also be given intrathecally on day 8 of week 1, week 3, week 5, week 7 and week 9.

DRUG

Motexafin gadolinium

* Administered to the first five patients enrolled on trial, MGd will be given at 5 mg/kg q day x2 doses (completed on 2 consecutive days 1 to 2 weeks prior to day of cycle 1) to be followed by a non-infused MRI (without contrast) 1-5 hours after 2nd MGd dose (to evaluate for MGd tumor selective uptake). * For induction chemotherapy, MGd 10 mg/kg will be given intravenously on day 8 of each cycle. MGd will be given immediately after Rituxan. * During radiation therapy, MGd will be administered at 5 mg/kg 2-5 hours prior to WBRT, daily for the first 10 days (fractions) and then every other day of radiation thereafter.

DRUG

Procarbazine hydrochloride

Taken orally, 100 mg/m2 days 1-7 of the 1st, 3rd, and 5th cycles of induction therapy.

DRUG

Vincristine sulfate

Administered by IV at a dose of 1.4mg per meter squared on weeks 1, 3, 5, 7 and 9.

RADIATION

Radiation therapy

Given at weeks 11 through 16.

Sponsors & Collaborators

• Pharmacyclics LLC.

  collaborator INDUSTRY

• Northwestern University

  lead OTHER

Principal Investigators

• Andrew M. Evens, DO, MS · Robert H. Lurie Cancer Center

• Jeffrey J. Raizer, MD · Robert H. Lurie Cancer Center

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-11-30