Trial Information

Phase I/II Study of the Combination of 5-azacitidine With Lenalidomide in Patients With High Risk Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML)

The Study Drugs:

Azacitidine is designed to block certain proteins that stop the function of tumor-fighting
genes. By blocking the "bad" proteins, the tumor-fighting genes may be able to work better.

Lenalidomide is designed to change the immune system. It may also interfere with the
development of tiny blood vessels that help support tumor growth. Therefore, in theory, it
may decrease or prevent the growth of cancer cells.

Study Groups:

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. Up to 6 groups of 3-6 participants will be
enrolled in the Phase 1 portion of the study, and up to 40 participants will be enrolled in
Phase 2.

If you are enrolled in the Phase 1 portion, the dose of lenalidomide you receive will depend
on when you joined this study. The first group of participants will receive the lowest dose
level of lenalidomide. Each new group will receive a higher dose of lenalidomide than the
group before it, if no intolerable side effects were seen. This will continue until the
highest tolerable dose of lenalidomide is found.

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

All participants will receive the same dose level of azacitidine.

Study Drug Administration:

Each study "cycle" will be about 3-8 weeks, depending on how well you tolerate the drugs,
any side effects that you may have, and how your blood count and bone marrow recovers.

On Days 1-5 of every cycle, you will receive azacitidine by vein over 15-30 minutes.

If you are enrolled in Phase 2 of the study, on Days 6-15 of every cycle, you will take
capsules of lenalidomide by mouth.

You should swallow lenalidomide capsules whole with a cup (about 8 ounces) of water at the
same time each day. Do not break, chew, or open the capsules. If you miss a dose of
lenalidomide, take it as soon as you remember on the same day. If you miss taking your dose
for the entire day, take your regular dose the next scheduled day (do NOT take double your
regular dose to make up for the missed dose). If you take more than the prescribed dose of
lenalidomide, you should seek emergency medical care if needed and contact study staff right
away. Any unused lenalidomide should be returned as instructed through the RevAssist®
program.

Any woman who can become pregnant should wear gloves if touching the lenalidomide capsules.

Your dose of study drugs may be lowered if you experience side effects.

You may be given drugs to help prevent side effects, such as nausea, vomiting, and/or
diarrhea. The doctor will tell you more about what drugs you may receive.

Study Visits:

At every study visit, you will be asked about any other drugs and/or treatments you may be
receiving and about any side effects you may be having.

One (1) time during each week of Cycle 1:

- Your medical history will be recorded.

- You will have a physical exam.

- Blood (about 1-2 tablespoons) will be drawn for routine tests.

On Days 21 and 28 of Cycle 1 (+/- 3 days), you will have a bone marrow aspiration performed
to check the status of the disease. You will then have a bone marrow aspiration performed
every 7-14 days for the rest of the study. If at any point the disease appears to go into
remission, you will then have a bone marrow aspiration performed every 1-3 cycles.

Before Day 1 of Cycles 2 and beyond:

- Your medical history will be recorded.

- You will have a physical exam.

- Blood (about 1-2 tablespoons) will be drawn for routine tests.

Pregnancy Testing:

If you are a woman who is able to become pregnant, you will have blood (about 1-2
tablespoons) or urine pregnancy tests 1 time a week for the first 4 weeks of the study, then
every 4 weeks while on study, when you stop the study, and 4 weeks after you are off study.

If you are a woman who is able to become pregnant and your menstrual cycles are irregular,
you will have blood (about 1-2 tablespoons) or urine pregnancy test 1 time a week for the
first 4 weeks, then every 2 weeks while on study, when you stop the study, and 2 and 4 weeks
after you are off study.

Length of Study:

You may receive azacitidine for up to 12 cycles (about 12-18 months). You may receive
lenalidomide as part of this study for as long as you are benefitting. You will be taken off
study if the disease gets worse or you experience intolerable side effects.

This is an investigational study. Both azacitidine and lenalidomide are FDA approved and
commercially available for the treatment of MDS. Azacitidine is not FDA approved or
commercially available for treatment of AML. The combination as used in this study is
investigational.

Up to 88 participants will take part in this study. All will be enrolled at MD Anderson.