Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients With Relapsed and Refractory Lymphoma

Phase I:

The Study Drugs:

Both panobinostat and everolimus are designed to block cancer cells from multiplying.
Everolimus may also stop the growth of new blood vessels that help tumor growth. As a
result, the cancer cells may grow more slowly or die.

Study Groups:

If you are found to be eligible to take part in this phase of the study, you will be
assigned to a study group based on when you joined this study. Up to 5 groups of 3-6
participants will be enrolled in this phase of the study.

If you are enrolled in this phase of the study, the dose of study drugs you receive will
depend on when you joined this study. The first group of participants will receive the
lowest dose level of the study drugs. Each new group may receive a higher dose of study
drugs than the group before it, if no intolerable side effects were seen. This will
continue for up to 5 combinations of the study drugs, until the highest tolerable dose of
study drugs in combination is found.

Up to 2 dose levels of everolimus and up to 4 dose levels of panobinostat will be tested in
this phase of the study. This is up to 5 different dose combinations of everolimus and
panobinostat. (The dose of both drugs does not get raised in every dose level, but
sometimes only 1 drug's dose gets raised.)

Study Drug Administration

Panobinostat:

You will take panobinostat by mouth 3 times a week during each cycle. Cycles in this study
are 28 days long.

You should take panobinostat with 1 cup (8 ounces) of water at about the same time each day
that you take it.

If you miss a dose of panobinostat, take it as soon as you remember it on the same day.
However, if more than 12 hours have passed since you were supposed to take the dose, you
should skip that day's dose. In that case, wait to take panobinostat until the next
scheduled treatment day.

Everolimus:

You will take everolimus every day, at about the same time in the morning. You will take it
by mouth with 1 cup (8 ounces) of water. You should take everolimus either with no food or
drink except water ("fasting") or with no more than a light, fat-free meal.

Examples of light, fat-free meals include cereal with fat-free milk, a fat-free muffin,
toast, a bagel with fat-free spread, or fruit salad.

The reason to avoid high-fat breakfasts while you are taking everolimus is to help the drug
get absorbed better by your body.

If you experience intolerable side effects, you must call your doctor right away. The doctor
may then lower the dose of study drug or take you off study.

Study Visits:

Within 7 days before the first dose of study drug:

- You will be asked about any drugs you may be taking.

- Blood (about 2 1/2 teaspoons) and urine will be collected for routine tests.

- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy
test.

On Day 1 of Cycle 1:

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

- You will be asked about any drugs you may be taking and any side effects that may have
occurred.

- Your performance status will be recorded.

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

- Blood (about 1 teaspoon) will be drawn for biomarker research.

- If your doctor thinks it is needed, urine will be collected for routine tests.

- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy
test.

On Days 1 and 5 of Cycle 1, you will have an ECG.

On Weeks 2, 3, and 4 of Cycle 1, blood (about 2 1/2 teaspoons) will be drawn for routine
tests.

On Week 2 of Cycle 1, blood (about 1 teaspoon) will be drawn for biomarker research.

On Day 1 of Cycle 2 and every cycle after that:

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

- You will be asked about any drugs you may be taking and any side effects that may have
occurred.

- Your performance status will be recorded.

- You will have an ECG (or more than 1 ECG if the doctor thinks it is needed).

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

- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy
test.

Every 8 weeks:

- You will have a PET scan to check the status of the disease.

- You will have a CT scan of your head and neck, chest, abdomen, and pelvis to check the
status of the disease.

Length of Study:

If you show benefit from taking the study drugs, you may receive up to 6 cycles. You will be
taken off study if you have intolerable side effects or the disease gets worse.

End-of-Treatment Visit:

After you stop taking the study drugs, you will return to the clinic for an end-of-treatment
visit:

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

- Your performance status will be recorded.

- You will have an ECG.

- You will be asked about any drugs you may be taking.

- Blood (about 3 1/2 teaspoons) will be collected for routine tests.

- You will have a PET scan to check the status of the disease.

- You will have a computed tomography (CT) scan of your head and neck, chest, abdomen,
and pelvis to check the status of the disease.

- If your doctor thinks it is needed, urine will be collected for routine tests.

- If the doctor thinks the disease has responded completely, you will have a bone marrow
biopsy and aspiration to confirm the complete response. To collect a bone marrow
biopsy/aspirate, an area of the hip is numbed with anesthetic, and a small amount of
bone marrow and bone is withdrawn through a large needle.

- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy
test.

Up to 18 patients will take part in Phase I of this study. All will be enrolled at M. D.
Anderson.

Phase II:

Study Drug Administration

Panobinostat:

You will take panobinostat by mouth 3 times a week during each cycle. Cycles in this study
are 28 days long.

You should take panobinostat with 1 cup (8 ounces) of water at about the same time each day
that you take it.

Everolimus:

You will take everolimus every day, at about the same time in the morning. You will take it
by mouth with 1 cup (8 ounces) of water. You should take everolimus either with no food or
drink except water ("fasting") or with no more than a light, fat-free meal.

If you experience intolerable side effects, you must call your doctor right away. The doctor
may then lower the dose of study drug or take you off study.

Study Visits:

Within 7 days before the first dose of study drug:

- You will be asked about any drugs you may be taking.

- Blood (about 2 1/2 teaspoons) and urine will be collected for routine tests.

- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy
test.

On Day 1 of Cycle 1:

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

- You will be asked about any drugs you may be taking and any side effects that may have
occurred.

- Your performance status will be recorded.

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

- Blood (about 4 tablespoons) will be drawn for biomarker research (if blood was not
drawn for biomarker research at screening).

- If your doctor thinks it is needed, urine will be collected for routine tests.

- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy
test.

On Days 1 and 5 of Cycle 1, you will have an ECG.

On Weeks 2, 3, and 4 of Cycle 1, blood (about 2 1/2 teaspoons) will be drawn for routine
tests.

On Weeks 2 and 3 of Cycle 1, blood (about 4 tablespoons) will be drawn for biomarker
research.

On Day 1 of Cycle 2 and every cycle after that:

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

- You will be asked about any drugs you may be taking and any side effects that may have
occurred.

- Your performance status will be recorded.

- You will have an ECG (or more than 1 ECG if the doctor thinks it is needed).

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

- Women who are able to become pregnant will have a blood (about 1 tablespoon) pregnancy
test.

Every 8 weeks:

- You will have a PET scan to check the status of the disease.

- You will have a CT scan of your head and neck, chest, abdomen, and pelvis to check the
status of the disease.

Up to 42 patients will take part in this phase of this study. All will be enrolled at M. D.
Anderson.

This is an investigational study. Panobinostat is not FDA approved or commercially
available. At this time the drug is being used in research only. Everolimus is FDA
approved and commercially available for the treatment of renal cell carcinoma. Using
everolimus in combination with panobinostat in patients with lymphoma is investigational.