Phase I Study of Panobinostat Plus ICE Chemotherapy Followed by a Randomized Phase-II Study of ICE Compared With Panobinostat Plus ICE for Patients With Relapsed and Refractory Classical Hodgkin Lymphoma
Phase I:
The Study Drugs:
Panobinostat is designed to block the function of enzymes that are found inside cancer
cells. These enzymes trigger cells to grow and multiply out of control. By blocking these
enzymes, it may slow down the growth of or kill cancer cells.
Ifosfamide is designed to slow or stop the growth of cancer cells.
Carboplatin is designed to interfere with the growth of cancer cells by stopping cell
division, which may cause the cells to die.
Etoposide is designed to block cell growth.
Baseline Tests:
If you are found to be eligible to take part in this study, the following tests and
procedures will be performed about 7 days before the first dose of the study drug:
- You will have a physical exam, including measurement of your height, weight, and vital
signs (blood pressure and heart rate).
- You will have 1 electrocardiogram (ECG -- a test that measures the electrical activity
of the heart).
- Blood (about 2 1/2 teaspoons) will be drawn for routine tests.
- Blood (about 2 teaspoons) will be drawn for biomarker testing. Biomarkers are chemical
"markers" in the blood/tissue that may be related to your reaction to the study drug.
- Women who are able to become pregnant must have a negative blood (about 1 1/2
teaspoons) pregnancy test.
Study Groups:
You will be assigned to a dose level of panobinostat based on when you join this study. Up
to 2 dose levels of panobinostat will be tested. Up to 6participants will be enrolled at
each dose level. The first group of participants will receive the lowest dose level. Each
new group will receive a higher dose than the group before it, if no intolerable side
effects were seen. This will continue until the highest tolerable dose of panobinostat is
found.
All participants will receive the same dose level of ICE.
Once the highest tolerable dose is found, up to 20 extra participants, called the expansion
group, will receive the study drugs at that dose.
Study Drug Administration:
Each cycle is 14 days.
ICE Administration:
On Day 1 (+/- 2 days) of Cycles 1-3, you will receive ifosfamide by vein over 24 hours.
On Day 1 (+/- 2 days) of Cycles 1-3, you will receive carboplatin by vein over 1 hour.
On Days 1-3 (+/- 2 days) of Cycles 1-3, you will receive etoposide by vein over 2 hours.
You will also receive mesna to help prevent side effects. On Day 1 (+/- 2 days) of Cycles
1-3, you will receive mesna by vein over 12 hours.
You will also receive pegfilgrastim to help prevent side effects. Beginning 24-48 hours
after the completion of chemotherapy of Cycles 1-3, you will take pegfilgrastim through a
needle under the skin.
Panobinostat Administration:
You will take panobinostat by mouth starting Day -6 of Cycle 1 (6 days before your first
dose of ICE). You will take the panobinostat on Days -6, -4, and -2 of Cycle 1 and Days 1,
3, 5, 8, 10, and 12 of Cycles 1 and 2.
If you are in the expansion group, you will take panobinostat by mouth starting Day -6 of
Cycle 1 (6 days before your first dose of ICE). You will take the panobinostat on Days -6,
-4, and -2 of Cycle 1 and Days 1, 3, and 5 of Cycles 1 and 2.
You should take panobinostat around the same time each day with 1 cup (8 ounces) of water.
You should swallow the capsules whole and not chew them. You must avoid grapefruit or
grapefruit juice and seville (sour) oranges while on study.
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 dosing day.
Study Visits:
On Days -6 and -2 of Cycle 1, you will have 2 ECGs.
Within 7 days before each ICE therapy:
- You will have a physical exam, including measurement of your height, weight, and vital
signs.
- Blood (about 2 1/2 teaspoons) will be drawn for routine tests.
- You will be asked if you have had any side effects.
One (1) time a week, blood (2 1/2 teaspoons) will be drawn for routine tests.
On Day 8 of Cycle 1 (±1 day), blood (about 2 teaspoons) will be drawn for biomarker testing.
Biomarkers are chemical "markers" in the blood/tissue that may be related to your reaction
to the study drug.
On Day 1 of Cycles 2 and beyond, you will have an ECG.
After Cycle 3:
- You will have a CT scan of your head and neck, chest, abdomen, and pelvis to check the
status of the disease.
- If your bone marrow was positive at screening, you will have a PET scan to check the
status of the disease.
Length of Study:
You be on study for up to 3 cycles (about 42 days). You will be taken off study early if the
disease worsens or you experience intolerable side effects.
End-of-Study Visit:
After you are off study, you will have an end-of-study visit at which the following will be
performed:
- You will have a physical exam, including measurement of your weight and vital signs.
- You will have an ECG.
This is an investigational study. Panobinostat is not FDA approved or commercially
available. It is currently being used for research purposes only.
ICE is FDA approved and commercially available for the treatment of several types of
lymphoma, including relapsed and refractory Hodgkins lymphoma. The combination of
panobinostat and ICE for the treatment of Hodgkin's lymphoma is investigational.
Up to 102 patients will take part in this study. All will be enrolled at MD Anderson.
Phase II:
The Study Drugs:
Panobinostat is designed to block the function of enzymes that are found inside cancer
cells. These enzymes trigger cells to grow and multiply out of control. By blocking these
enzymes, it may slow down the growth of or kill cancer cells.
Ifosfamide is designed to slow or stop the growth of cancer cells.
Carboplatin is designed to interfere with the growth of cancer cells by stopping cell
division, which may cause the cells to die.
Etoposide is designed to block cell growth.
Baseline Tests:
If you are found to be eligible to take part in this study, the following tests and
procedures will be performed about 7 days before the first dose of the study drug:
- You will have a physical exam, including measurement of your height, weight, and vital
signs (blood pressure and heart rate).
- You will have 1 electrocardiogram (ECG -- a test that measures the electrical activity
of the heart).
- Blood (about 2 1/2 teaspoons) will be drawn for routine tests.
- Blood (about 2 teaspoons) will be drawn for biomarker testing. Biomarkers are chemical
"markers" in the blood/tissue that may be related to your reaction to the study drug.
- Women who are able to become pregnant must have a negative blood (about 1 1/2
teaspoons) pregnancy test.
Study Groups:
You will be randomly assigned (as in the flip of a coin) to 1 of 2 groups.
- If you are in Group 1, you will receive ICE.
- If you are in Group 2, you will receive ICE and panobinostat.
Study Drug Administration:
Each cycle is 14 days.
ICE Administration:
On Day 1 (+/- 2 days) of Cycles 1-3, you will receive ifosfamide by vein over 24 hours.
On Day 1 (+/- 2 days) of Cycles 1-3, you will receive carboplatin by vein over 1 hour.
On Days 1-3 (+/- 2 days) of Cycles 1-3, you will receive etoposide by vein over 2 hours.
You will also receive mesna to help prevent side effects. On Day 1 (+/- 2 days) of Cycles
1-3, you will receive mesna by vein over 12 hours.
You will also receive pegfilgrastim to help prevent side effects. Beginning 24-48 hours
after the completion of chemotherapy of Cycles 1-3, you will take pegfilgrastim through a
needle under the skin.
Panobinostat Administration:
If you are in a group that will receive panobinostat, you will take panobinostat by mouth
starting Day -6 of Cycle 1 (6 days before your first dose of ICE). You will take the
panobinostat on 3 times a week during Cycles 1 and 2 (Days -6, -4, and -2 of Cycle 1 and
Days 1, 3, 5, 8, 10, and 12 of Cycles 1 and 2).
You should take panobinostat around the same time each day with 1 cup (8 ounces) of water.
You should swallow the capsules whole and not chew them. You must avoid grapefruit or
grapefruit juice and seville (sour) oranges while on study.
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 dosing day.
Study Visits:
On Days -6 and -2 of Cycle 1, you will have 2 ECGs.
Within 7 days before each ICE therapy:
- You will have a physical exam, including measurement of your height, weight, and vital
signs.
- Blood (about 2 1/2 teaspoons) will be drawn for routine tests.
- You will be asked if you have had any side effects.
One (1) time a week, blood (2 1/2 teaspoons) will be drawn for routine tests.
On Day 8 of Cycle 1 (±1 day), blood (about 2 teaspoons) will be drawn for biomarker testing.
Biomarkers are chemical "markers" in the blood/tissue that may be related to your reaction
to the study drug.
On Day 1 of Cycles 2 and beyond, you will have an ECG.
After Cycle 3:
- You will have a CT scan of your head and neck, chest, abdomen, and pelvis to check the
status of the disease.
- If your bone marrow was positive at screening, you will have a PET scan to check the
status of the disease.
Length of Study:
You be on study for up to 3 cycles (about 42 days). You will be taken off study early if the
disease worsens or you experience intolerable side effects.
End-of-Study Visit:
After you are off study, you will have an end-of-study visit at which the following will be
performed:
- You will have a physical exam, including measurement of your weight and vital signs.
- You will have an ECG.
This is an investigational study. Panobinostat is not FDA approved or commercially
available. It is currently being used for research purposes only.
ICE is FDA approved and commercially available for the treatment of several types of
lymphoma, including relapsed and refractory Hodgkins lymphoma. The combination of
panobinostat and ICE for the treatment of Hodgkin's lymphoma is investigational.
Up to 102 patients will take part in this study. All will be enrolled at MD Anderson.
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Phase I Maximal Tolerated Dose (MTD) of Panobinostat + ICE
MTD defined by patient dose limiting toxicities (DLT) at each dose level, monitored for 14 days (1 cycle) from first dose of ICE.
Each cycle, 14 days from first dose of ICE
Yes
Yasuhiro Oki, MD
Principal Investigator
UT MD Anderson Cancer Center
United States: Food and Drug Administration
2010-0065
NCT01169636
January 2011
Name | Location |
---|---|
UT MD Anderson Cancer Center | Houston, Texas 77030 |