Trial Information

A Phase I/II Clinical Trial of Fludarabine, Bendamustine, and Rituximab (FBR) in Previously Treated Patients With Chronic Lymphocytic Leukemia (CLL)

The Study Drugs:

Fludarabine and bendamustine are designed to damage the DNA (genetic material) of cancer
cells, which may cause the cancer cells to die.

Rituximab is designed to attach to cancer cells and damage them, which may cause the cancer
cells to die. It is also designed to cause the immune system to attack cancer cells.

Study Drug Dose Levels:

If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you joined this study. One (1) to 8 groups with 3-6 participants will be
enrolled in the Phase 1 portion of the study, and up to 58 participants will be enrolled in
Phase 2.

If you are enrolled in Phase 1, the dose of bendamustine you receive will depend on when you
joined this study. The first group will receive the lowest dose. The next group will
receive a higher dose, if the number and type of side effects was low or none. The dose of
bendamustine will be increased for each new group until the highest tolerable dose is found.

If you are enrolled in Phase 2, you will receive bendamustine at the highest dose that was
tolerated in Phase 1.

All participants in both phases of the study will start out with the same dose levels of
fludarabine and rituximab.

If side effects occur, the study doctor may decide to lower your doses of study therapy. If
you have side effects during a dose, the study staff will observe you for any other problems
for 2 hours after the dose.

Study Drug Administration:

Cycles in this study are 4 weeks. All 3 study drugs are given by vein.

Cycle 1:

- On Days 1-3, bendamustine will be given over 30 minutes.

- On Days 2-4, fludarabine will be given over 30 minutes.

- On Day 4, rituximab will be given over 6-8 hours.

Cycles 2-6:

- On Day 1, rituximab will be given at a higher dose than in Cycle 1. If you tolerated
the Cycle 1 dose well, your Cycles 2-6 rituximab doses may be given over 2-4 hours.

- On Days 1-3, fludarabine will be given over 30 minutes.

- On Days 1-3, bendamustine will be given over 30 minutes.

Other Drugs:

You will be given Tylenol (acetaminophen) and Benadryl (diphenhydramine hydrochloride) to
take by mouth 30-60 minutes before every dose of rituximab (Cycles 1-6). These drugs are
given to lower the risk of side effects.

Study Visits:

Once a week in Cycle 1 and every 2-4 weeks in Cycles 2-6, blood (about 1 tablespoon) will be
drawn for routine tests.

Before Cycles 1-6, you will also have a physical exam, including measurement of your vital
signs. You will be asked about any side effects you may have had.

Before Cycle 4, the following tests and procedures will be performed:

- You will have a physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests.

- You will have a bone marrow aspiration and biopsy to check the status of the disease.

- If the doctor thinks it is needed, you will have a CT scan of the neck, chest, abdomen,
and pelvis to check the status of the disease.

Length of Study Participation:

You may receive up to 6 cycles of study treatment. The study treatment will be stopped
early if the disease gets worse or you experience any intolerable side effects.

End-of-Treatment Visit:

After Cycle 6 (or earlier if you stop early), the following tests and procedures will be
performed:

- You will have a physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests.

- You will have a bone marrow aspiration and biopsy to check the status of the disease.

- If the doctor thinks the disease has completely responded, you will have a CT scan of
the neck, chest, abdomen, and pelvis to confirm the response.

Follow-Up Visits:

You will have follow-up visits at the end of Month 6 and Year 1 after your last dose of
study drugs, and once a year until you start a new cancer treatment. The same tests will be
performed as at the end-of-treatment visit. Starting at Year 3, the follow-up tests and
procedures can be done by your local doctor if that is more convenient to you.

You should tell your study doctor or staff if you start another cancer treatment after the
study. If that occurs, your follow-up in this study will stop.

This is an investigational study. Both fludarabine and bendamustine are commercially
available and FDA approved to treat CLL. Rituximab is commercially available and FDA
approved to treat lymphoma. The use of these drugs together in this study is
investigational.

Up to 82 patients will take part in this study. All will be enrolled at MD Anderson.