Ignite Creation Date:
2024-05-05 @ 10:42 PM
Last Modification Date:
2024-10-26 @ 10:23 AM
Study NCT ID:
NCT01169636
Status:
COMPLETED
Last Update Posted:
2021-01-06
First Post:
2010-07-22
Brief Title:
Panobinostat Plus Ifosfamide Carboplatin and Etoposide ICE Compared With ICE For Relapsed Hodgkin Lymphoma
Sponsor:
MD Anderson Cancer Center
Organization:
MD Anderson Cancer Center
Study Overview
Official Title:
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
Status:
COMPLETED
Status Verified Date:
2020-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Objectives
Primary objective
Phase-I To determine the maximal tolerated dose MTD of panobinostat LBH589 Ifosfamide Mesna Carboplatin and Etoposide ICE combination
Randomized Phase-II To estimate the complete response CR rate in patients with relapsed and refractory classical Hodgkins Lymphoma HL receiving ICE versus PANOBINOSTAT plus ICE therapy
Secondary Objectives
To assess the safety and tolerability of the novel combination of PANOBINOSTAT LBH589 plus ICE versus ICE in patients with relapsed and refractory HL
To estimate the overall response rate CR partial response PR
To estimate the success rate of stem cell collection in patients eligible for stem cell transplant
To estimate the percentage of patients who subsequently undergo autologous stem cell transplantation ASCT
To estimate the event free survival EFS at 1 year after randomization
To determine pretreatment expression level of histone deacetylases HDAC1 HDAC2 and pSTAT3 and Signal transducer and activator of transcription protein pSTAT6 by Immunohistochemistry IHC and correlate the results with treatment response
Primary objective
Phase-I To determine the maximal tolerated dose MTD of panobinostat LBH589 Ifosfamide Mesna Carboplatin and Etoposide ICE combination
Randomized Phase-II To estimate the complete response CR rate in patients with relapsed and refractory classical Hodgkins Lymphoma HL receiving ICE versus PANOBINOSTAT plus ICE therapy
Secondary Objectives
To assess the safety and tolerability of the novel combination of PANOBINOSTAT LBH589 plus ICE versus ICE in patients with relapsed and refractory HL
To estimate the overall response rate CR partial response PR
To estimate the success rate of stem cell collection in patients eligible for stem cell transplant
To estimate the percentage of patients who subsequently undergo autologous stem cell transplantation ASCT
To estimate the event free survival EFS at 1 year after randomization
To determine pretreatment expression level of histone deacetylases HDAC1 HDAC2 and pSTAT3 and Signal transducer and activator of transcription protein pSTAT6 by Immunohistochemistry IHC and correlate the results with treatment response
Detailed Description:
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 12 teaspoons will be drawn for routine tests
Women who are able to become pregnant must have a negative blood about 1 12 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 2 - 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 days 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 12 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 12 teaspoons will be drawn for routine tests
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 positron emission tomography 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 Hodgkins 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 12 teaspoons will be drawn for routine tests
Women who are able to become pregnant must have a negative blood about 1 12 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 2 - 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 and 5 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 days 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 12 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 12 teaspoons will be drawn for routine tests
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 Hodgkins lymphoma is investigational
Up to 102 patients will take part in this study All will be enrolled at MD Anderson
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 12 teaspoons will be drawn for routine tests
Women who are able to become pregnant must have a negative blood about 1 12 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 2 - 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 days 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 12 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 12 teaspoons will be drawn for routine tests
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 positron emission tomography 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 Hodgkins 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 12 teaspoons will be drawn for routine tests
Women who are able to become pregnant must have a negative blood about 1 12 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 2 - 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 and 5 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 days 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 12 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 12 teaspoons will be drawn for routine tests
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 Hodgkins lymphoma is investigational
Up to 102 patients will take part in this study All will be enrolled at MD Anderson
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2012-01779 | REGISTRY | NCI CTRP | None |