Phase I/II of Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients With Relapsed and Refractory Lymphoma
Phase I/II of Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients With Relapsed and Refractory Lymphoma
Objectives:
Primary:
Secondary:
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.
You should not consume grapefruit products or Seville (sour) oranges while you are on study, because they may interact with everolimus.
Study Visits:
Within 7 days before the first dose of study drug:
On Day 1 of Cycle 1:
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:
Every 8 weeks:
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:
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.
Up to 18 patients will take part in this phase of this study. All will be enrolled at MD Anderson.
Phase II:
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 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.
You should not consume grapefruit products or Seville (sour) oranges while you are on study, because they may interact with everolimus.
Study Visits:
Within 7 days before the first dose of study drug:
On Day 1 of Cycle 1:
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:
Every 8 weeks:
Length of Study:
You may continue receiving the study drugs for as long as you are benefitting. 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:
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.
Up to 42 patients will take part in this phase of this study. All will be enrolled at MD Anderson.
Inclusion Criteria:
Exclusion Criteria: