Study of Grifola Frondosa (Maitake), Azacitidine, and Lenalidomide

Study Drugs:

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

Lenalidomide is designed to change the body's immune system. It may also interfere with the
development of tiny blood vessels that help support tumor growth. This may decrease the
growth of cancer cells.

Grifola frondosa extract is a natural substance taken from maitake mushrooms. Researchers
want to learn if it can cause the body's immune system to react against cancer.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to receive
either azacitidine and lenalidomide, azacitidine and Grifola frondosa, or azacitidine,
lenalidomide, and Grifola frondosa at a dose level based on when you joined this study.

Up to 4 dose levels of azacitidine and lenalidomide will be tested. One dose level of
azacitidine and Grifola frondosa will be tested. At the beginning of the study, 3-6
participants will be enrolled at each dose level of the study drug combinations. The first
group of participants will receive the lowest dose level of azacitidine and lenalidomide.
Each new group will receive a higher dose of the study drug combination than the group
before it, if no intolerable side effects were seen. This will continue until the highest
tolerable dose of the study drug combination is found.

After the highest dose of the azacitidine and lenalidomide combination is found and the
combination of azacitine and Grifola frondosa is shown to be safe, new participants
enrolling in this study will begin receiving Grifola frondosa along with azacitidine and
lenalidomide. Up to 2 dose levels will be tested. The first group of participants will
receive the lowest dose level of lenalidomide. The next group will receive a higher dose of
lenalidomide than the group before it, if no intolerable side effects were seen. The doses
of azacitidine and Grifola frondosa will stay the same.

The dose of the study drug combination that you receive may be lowered if you have any
intolerable side effects.

Study Drug Administration:

A study drug "cycle" is 28 days.

On Days 1-5 of each Cycle, you will receive azacitidine either under the skin or by vein.
If you receive azacitidine as an injection under the skin, you will receive it over 10
minutes. If you receive azacitidine by vein, you will receive it over 40 minutes.

On Day 2 of Cycle 1, you will begin taking lenalidomide 1 time each day until Day 21, then
you will have a 7 day-rest period. For Cycle 2 and every cycle after that, you will take
lenalidomide 1 time each day on Days 1-21 followed by a 7-day rest period. Lenalidomide is
a capsule that you will take by mouth with water. The capsules should be swallowed whole.
You should not break, chew, or open the capsules.

If you are assigned to receive Grifola frondosa, you will also begin taking Grifola frondosa
2 times each day on Day 2 of Cycle 1 if you are also taking azacitidine. If you are also
taking azacitidine and lenalidomide, you will begin taking Grifola frondosa on Day 3 of
Cycle 1. You will take Grifola frondosa 2 times each day until Day 21, then you will have a
7-day rest period. For every cycle after that, you will take Grifola frondosa 2 times each
day on Days 1-21, followed by a 7-day rest period. Grifola frondosa is a liquid extract
that comes in a glass bottle. Your dose of Grifola frondosa will be based on when you joined
the study and your body weight.

Expansion Groups:

After the highest tolerable dose of each study drug combination is found, 42 additional
participants will be enrolled in 3 expansion groups (14 in each group), one group for each
study drug combination at the highest tolerable dose or a dose level that has been shown to
be safe.

Study Visits:

The following tests and procedures will be performed within 7 days before your first dose of
study drug:

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) and urine will be collected for routine tests.

Women who are able to have children must have a negative blood (about 1 teaspoon) pregnancy
test within 10 to 14 days before the first dose of the study drug combination and again
within 24 hours before receiving lenalidomide.

Before you begin each cycle, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) and urine will be collected for routine tests.

- You will be asked about any side effects you may be having.

- If the study doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to
measure tumor markers.

- Women who are able to have children will have a blood pregnancy test.

Every week during Cycles 1 and 2, blood (about 2 teaspoons) will be drawn for routine tests.

Women who are able to have children will have a blood (about 1 teaspoon) pregnancy test
every week during Cycle 1.

At the end of every 2 cycles (Cycles 2, 4, 6, and so on), you will have a CT, MRI, PET scan,
and/or x-ray to check the status of the disease.

If you are in the one of the Expansion Groups, blood (about 6 teaspoons each time) will be
drawn for biomarker testing before you take the first dose of study drug, on Days 21and 28
of Cycle 1, 1 time during each cycle after that, and at the end-of-study visit.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drugs if the disease gets worse or
intolerable side effects occur.

End-of-Study Visit:

Within 30 days after your last dose of the study drug combination, you will have an
end-of-study visit. The following tests and procedures performed:

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) and urine will be collected for routine tests.

- You will be asked about any side effects you may be having.

- If the study doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to
measure tumor markers.

- If the study doctor thinks it is needed, you will have a chest x-ray, CT, MRI, and/or
PET scan to check the status of the disease.

- Women who are able to have children will have a blood pregnancy test.

This is an investigational study. Grifola frondosa extract is not FDA approved for any
usage. Its use in this study is investigational. Azacitidine and lenalidomide are FDA
approved and commercially available for the treatment of multiple myeloma and
myelodysplastic syndrome. The use of the study drug combination (Grifola frondosa,
azacitidine, and lenalidomide) is currently being used for research purposes only.

Up to 96 patients will take part in this study. All will be enrolled at M. D. Anderson.