Trial Information

Randomized, Double-Blind, Placebo Controlled Trial of Voraxaze™ in Patients With a Delayed MTX Clearance

Researchers want to learn how glucarpidase may impact patients' length of stay in the
hospital, kidney function, and quality of life. Also, researchers want to learn if
glucarpidase may decrease the incidence of neutropenic fever, which may decrease the use of
antibiotics by vein to treat this kind of fever.

MTX is a high-dose chemotherapy drug that reduces the supply of an important vitamin
(folate) required for the growth of cancer cells. In patients with delayed clearance of MTX
from the body, there is a risk of more frequent or severe side effects from the drug.

Glucarpidase is a drug that breaks down MTX in the blood, causing the drug to be less toxic
and decreasing levels of the drug in the blood.

Before you can start treatment on this study, you will have "screening tests." These tests
will help the doctor decide if you are eligible to take part in this study. Your complete
medical history will be recorded. You will have a physical exam, including measurement of
your vital signs (temperature, pulse, breathing rate, and blood pressure). You will have
blood drawn (about 3 teaspoons) for routine tests. You will also have blood drawn (about 1
teaspoon), right before treatment starts, 28 days after the first dose of study drug in each
cycle, and at the end of the study to see if you have any antibodies (proteins in the body
that help fight infections and foreign substances in the body) to the study drug. Women who
are able to have children must have a negative blood pregnancy test. The blood used for the
pregnancy test will come from the sample taken for routine tests. (There is no additional
blood draw for the pregnancy test).

You may be given either glucarpidase or placebo (a drug that looks like glucarpidase but is
not active). Neither you nor the study doctor will know if you have been given glucarpidase
or placebo. This is called the blinded phase of this study. Before you can begin on this
study, if you are already suffering from side effects (because of difficulty with MTX
clearance), such as kidney toxicity, severe mucositis (redness and painful ulcers in the
mouth), and/or you have extremely high MTX levels, you will not be randomized and will
receive glucarpidase, not placebo. If this is the case, your doctor will know that you have
been given glucarpidase.

If you are found to be eligible to take part in this study, you will be assigned to 1 of 2
treatment groups, which will be based on the dose of MTX you received. You will then be
randomly assigned (as in the toss of a coin) to one of two treatment groups. Participants
in one group will receive glucarpidase. Participants in the other group will receive
placebo. There is a higher chance that you may receive glucarpidase than placebo because
for every patient that receives placebo, 2 patients will receive glucarpidase. The
glucarpidase or placebo dose that you may receive will be given by vein within 12 hours
after you have been found eligible to participate in this study. Glucarpidase or placebo
will be given during the first study cycle (after MTX treatment is completed, if after 72
hours your MTX levels are found to be high). You may receive additional doses of
glucarpidase (depending upon the level of MTX in your blood) up to a maximum of 2 doses. If
this is the case, the second dose will be given at least 24 hours after the first dose you
received.

Regardless of the treatment group that you are assigned to, you will continue to receive
standard treatment (fluids by vein with sodium acetate or sodium bicarbonate and leucovorin)
for high MTX levels. In future cycles of MTX, you may receive glucarpidase, if you continue
to experience a delay of MTX clearing from your body. The glucarpidase dose may be repeated
a maximum of 2 times in a given cycle of chemotherapy. The length of a cycle of chemotherapy
will vary, depending on the dose of MTX and the regimen the patient is receiving. One cycle
of treatment with glucarpidase is at least 24 hours apart.

You will be asked to fill out several questionnaires regarding your quality of life. These
questionnaires will ask about your level of pain, fatigue, nausea, sleep disturbances, etc.
They will be given during the first study cycle only (before the study drug is given and
daily during the first study cycle). They will take about 5 minutes to complete each time.

You will also have blood drawn (about 3 teaspoons each), at different times, so that study
doctors can monitor your kidney function and liver function, depending on your clinical
condition. These blood samples will be drawn at least twice a week while you are on this
study. You will again have blood drawn for the presence of antibodies 14 days after
treatment with glucarpidase, before every cycle of MTX treatment, and at the end of this
study.

You will be taken off this study if your disease gets worse, you experience intolerable side
effects, or you completed planned therapy (a maximum of 6 cycles of study drug). At the end
of this study, your complete medical history will again be recorded. You will have a
physical exam, including measurement of your vital signs. You will also have blood drawn
(about 1 teaspoon) for routine tests.

This is an investigational study. Glucarpidase is not FDA approved or commercially
available. The M. D. Anderson Institutional Review Board (IRB) has authorized the use of
glucarpidase for research only. The IRB is a committee made up of doctors, researchers, and
members of the community. The IRB is responsible for protecting the participants involved
in research studies and making sure all research is done in a safe and ethical manner.
Glucarpidase and placebo will be provided free of charge during this study. Up to 46
patients will take part in this study. All patients will be enrolled at M. D. Anderson.