Trial Information

A Randomized Trial of Rituximab vs Alemtuzumab vs Alemtuzumab + Rituximab as Consolidation Therapy for Patients With Chronic Lymphocytic Leukemia (CLL) With Evidence of Residual Disease Following Prior Chemo(Immuno)Therapy

Study Drugs:

Alemtuzumab and rituximab are both monoclonal antibodies. Monoclonal antibodies are proteins
designed to attach to a protein on the surface of the leukemia cell. By attaching to the
leukemia cell, monoclonal antibodies alert the immune system to target that cell and kill
it.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the roll of a dice) to 1 of 3 groups. Group 1 will receive rituximab alone. Group 2
will receive alemtuzumab alone. Group 3 will receive both drugs together.

At the beginning of the study, the chance of being assigned into any of the groups is about
equal. However, once enough participants are on study and the response rate in each group is
known, you will have a slightly better chance of being assigned to the group with the
highest response rate.

Study Drug Administration:

Group 1:

If you are in Group 1, rituximab will be given through a needle in your vein 1 time a week
for 4 weeks. The first time you receive rituximab, it will be given over about 4-6 hours.
Depending on any side effects you may have, the later infusions may be given over about 2-4
hours.

Before each dose of rituximab, you will receive drugs such as benadryl (diphenhydramine),
Tylenol (acetaminophen), and sometimes steroids (either by mouth or into your vein) to try
and prevent and/or help control side effects such as fevers and chills.

To help prevent infections, you will take the antibiotic valacyclovir (or a similar drug).
Valacyclovir is taken 1 time a day every day. Your doctor will describe this to you in more
detail.

Group 2:

If you are in Group 2, alemtuzumab will be given as an injection under your skin 3 times a
week for 13 weeks. You will have to come to the clinic for each dose, learn how to inject
it yourself, or have someone else taught how to inject you.

To help prevent infections, you will take the antibiotic trimethoprin/sulfamethoxazole
(SMX). Your doctor will tell you if you will take the tablet 2 times a day either 3 times a
week (Monday, Wednesday, and Friday) or 2 times a week (Saturday and Sunday). You will also
take either the antibiotic valganciclovir or valacyclovir. Valganciclovir tablets are taken
2 times every day. Valacyclovir is taken 1 time a day every day. You will continue to take
the antibiotics for at least 3 months after your last dose of alemtuzumab.

Group 3:

If you are in Group 3, rituximab will be given through a needle in your vein 1 time a week
for 4 weeks. The first time you receive the rituximab, it will be given over about 4-6
hours. Depending on any side effects you may have, the later infusions may be given over
about 2-4 hours.

Alemtuzumab will be given as an injection under your skin 3 times a week for 13 weeks. You
will have to come to the clinic for each dose, learn how to inject it yourself, or have
someone else taught how to inject you.

Before each dose of rituximab, you will receive drugs such as benadryl (diphenhydramine),
Tylenol (acetaminophen), and sometimes steroids (either by mouth or into your vein) to try
and prevent and/or help control side effects.

To help prevent infections, you will take the antibiotic trimethoprin/sulfamethoxazole
(SMX). Your doctor will tell you if you will take the tablet 2 times a day either 3 times a
week (Monday, Wednesday, and Friday) or 2 times a week (Saturday and Sunday). You will also
take either the antibiotic valganciclovir or valacyclovir. Valganciclovir tablets are taken
2 times every day. Valacyclovir is taken 1 time a day every day. You will continue to take
the antibiotics for at least 3 months after your last dose of alemtuzumab.

Study Visits:

Every week while you are receiving therapy, blood (about 1 tablespoon) will be drawn for
routine tests.

Six (6), 12, and 18 weeks (+/- 1 week) after you begin receiving the study drug(s) and then
every 6 months (+/- 1 month) after that, you will have bone marrow biopsies and/or aspirates
to check the status of the disease and to check for residual disease.

Every 6 months (+/- 3 months) after you have stopped receiving therapy, you will have a
physical exam and blood (about 1 tablespoon) will be drawn for routine tests.

If you are in Group 2 or 3, during Week 3 and 6, blood (about 1 teaspoon) will be drawn to
check for the cytomegalovirus (CMV) infection. This infection may occur in people with
weakened immune systems.

If your doctor thinks it is necessary, you will have a chest x-ray and/or other scans.

Length of Study:

If you are in Group 1, you will take the study drug for up to 4 weeks. If you are in Groups
2 or 3, you will take the study drug(s) for up to 13 weeks. You will be taken off treatment
early if you have intolerable side effects.

You will remain on study as long as the disease does not get worse.

This is an investigational study. Rituximab is FDA approved and commercially available for
non-Hodgkin's lymphoma. However, it is not approved for the treatment of CLL.

Alemtuzumab is FDA approved and commercially available. It has been approved for the
treatment of CLL when given by vein. It has not been approved to be given as an injection
under the skin or for treatment after chemotherapy.

Up to 100 patients will take part in this study. All will be enrolled at M. D. Anderson.