A Phase I/II Clinical Trial of Pomalidomide With Melphalan and Dexamethasone in Patients With Newly Diagnosed Untreated Systemic AL Amyloidosis
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose
level of pomalidomide, based on when you join this study. Up to 4 dose levels of
pomalidomide will be tested for the Phase I portion of this study. Up to 30 participants
will be enrolled at each dose level in the Phase I portion, and up to 24 participants will
be enrolled in Phase II. 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
pomalidomide is found.
If you are enrolled in the Phase II portion, you will receive pomalidomide at the highest
dose that was tolerated in the Phase I portion.
All participants will receive the same dose level of dexamethasone and melphalan. If
intolerable side effects are seen at the lowest dose level, then the melphalan dose will be
lowered.
Study Drug Administration:
Each cycle is 28 days.
Treatment Phase:
You will take pomalidomide pills by mouth on Days 1-21 of each cycle. You should take each
dose of pomalidomide at about the same time every day. Swallow the pomalidomide capsules
whole with water at the same time each day. Pomalidomide should be taken without food (at
least 2 hours before or 2 hours after a meal). Do not break, chew, or open the capsules. If
you miss a dose of pomalidomide, take it as soon as you remember on the same day. If you
miss taking your dose for the entire day, take your regular dose the next scheduled day (DO
NOT take double your regular dose to make up for the missed dose). You should tell the
study doctor and/or nurse right away about any missed doses of pomalidomide. If you take
more than the prescribed dose of pomalidomide, you should seek emergency medical care, if
needed, and contact the study staff right away. You will need to return any unused
pomalidomide and empty bottles to the clinic at each study visit.
On Days 1-4 of each cycle, you will take melphalan pills by mouth one time each day. You
should take melphalan in the morning at least 2 hours before or after a meal.
You will take dexamethasone pills on Days 1-4 of each cycle.
You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks. You will receive
a blood thinner to prevent blood clots. The study doctor will decide what type of blood
thinner you will receive.
Maintenance Phase:
You will take pomalidomide pills by mouth on Days 1-28 of each cycle during the maintenance
phase. You should take each dose of pomalidomide at about the same time every day. Swallow
the pomalidomide capsules whole with water, at the same time each day. Do not break, chew,
or open the capsules. If you miss a dose of pomalidomide, take it as soon as you remember
on the same day. If you miss taking your dose for the entire day, take your regular dose
the next scheduled day (DO NOT take double your regular dose to make up for the missed
dose). You should tell the study doctor and/or nurse right away about any missed doses of
pomalidomide. If you take more than the prescribed dose of pomalidomide, you should seek
emergency medical care, if needed, and contact the study staff right away. You will need to
return any unused pomalidomide and empty bottles to the clinic at each study visit.
You will also be given a study drug diary. Each time you take pomalidomide at home, you
should write down the date, time, and how many capsules or tablets you took. You should
bring the diary in with you at each study visit for the study doctor to review.
Study Visits:
At every visit you will be asked if you have had any side effects and to list any drugs you
may be taking.
Treatment Phase:
On Day 1 of Cycle 1:
- Your medical history will be reviewed and recorded.
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will be given the study drug diary.
- You will have an EKG and an ECHO.
- You will complete a questionnaire about the feeling in your hands.
- You will be asked about any joint pain you may be experiencing.
- Your lung function will be tested.
- The study doctor will look at your tongue to check the status of the disease.
- You will complete 2 questionnaires about quality-of-life, your general health, your
level of pain, and how the disease affects you. It will take about 15 minutes to
complete the questionnaires.
- Blood (about 1 tablespoon) and urine and/or feces (over 24 hours) will be collected to
check the status of the disease.
- Blood (about 1 tablespoon) will be drawn for genetic testing.
- Blood (about 1 tablespoon) will be drawn for routine tests. If you are able to become
pregnant, a pregnancy test will also be performed.
- If your doctor thinks it is necessary, you will have an ultrasound of the liver and/or
a biopsy of fatty tissue to check the status of the disease.
On Days 8 and 22 of Cycle 1:
-Blood (about 1 tablespoon) will be drawn for routine tests.
On Day 15 of Cycle 1:
- Your medical history will be reviewed and recorded.
- You will have a physical exam including measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will have an EKG.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will complete a questionnaire about your general health, your level of pain, and
how the disease affects you. It will take about 8 minutes to complete the
questionnaire.
On Day 1 of Cycles 2 and beyond:
- Your medical history will be reviewed and recorded.
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will have an EKG and an ECHO.
- You will complete a questionnaire about the feeling in your hands.
- You will be asked about any joint pain you may be experiencing.
- Your lung function will be tested.
- The study doctor will look at your tongue to check the status of the disease.
- You will complete 2 questionnaires about quality-of-life, your general health, your
level of pain, and how the disease affects you. It will take about 15 minutes to
complete the questionnaires.
- Blood (about 1 tablespoon) and urine and/or feces (over 24 hours) will be collected to
check the status of the disease.
- Blood (about 1 tablespoon) will be drawn for genetic testing.
- Blood (about 1 tablespoon) will be drawn for routine tests. If you are able to become
pregnant, a pregnancy test will also be performed.
- If your doctor thinks it is necessary, you will have an ultrasound of the liver, a
biopsy of fatty tissue, and/or a bone marrow aspiration to check the status of the
disease.
On Day 15 of Cycles 2 and beyond:
-You will complete a questionnaire about your general health, your level of pain, and how
the disease affects you. It will take about 8 minutes to complete the questionnaire.
Maintenance Phase:
On Day 1 of Cycle 1:
- Your medical history will be reviewed and recorded.
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will have an ECHO.
- You will complete a questionnaire about the feeling in your hands.
- You will be asked about any joint pain you may be experiencing.
- Your lung function will be tested.
- The study doctor will look at your tongue to check the status of the disease.
- You will complete 2 questionnaires about quality-of-life, your general health, your
level of pain, and how the disease affects you. It will take about 15 minutes to
complete the questionnaires.
- Blood (about 1 tablespoon) and urine and/or feces (over 24 hours) will be collected to
check the status of the disease.
- Blood (about 1 tablespoon) will be drawn for genetic testing.
- Blood (about 1 tablespoon) will be drawn for routine tests. If you are able to become
pregnant, a pregnancy test will also be performed.
- If your doctor thinks it is necessary, you will have an ultrasound of the liver and/or
a biopsy of fatty tissue to check the status of the disease.
On Day 1 of Cycles 2 and beyond:
- Your medical history will be reviewed and recorded.
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will complete 2 questionnaires about quality-of-life, your general health, your
level of pain, and how the disease affects you. It will take about 15 minutes to
complete the questionnaires.
- Blood (about 1 tablespoon) and urine (over 24 hours) will be collected to check the
status of the disease.
- Blood (about 1 tablespoon) will be drawn for routine tests. If you are able to become
pregnant, a pregnancy test will also be performed.
Length of Study:
The Treatment Phase of the study will take about 6 months to complete. If the study doctor
thinks you are benefiting from the study drug combination, you will go into the Maintenance
Phase. You can continue taking the study drug(s) until you experience intolerable side
effects, the disease gets worse, or the study doctor thinks it is in your best interests to
stop.
End-of-Treatment Visit:
If you go off study for any reason, you will have an end-of-treatment visit within 4 weeks
after the last dose of the study drug combination and the following tests and procedures
will be performed:
- Your medical history will be reviewed and recorded.
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- You will complete a questionnaire about the feeling in your hands.
- You will be asked about any joint pain you may be experiencing.
- Your lung function will be tested.
- The study doctor will look at your tongue to check the status of the disease.
- You will complete 2 questionnaires about quality-of-life, your general health, your
level of pain, and how the disease affects you. It will take about 15 minutes to
complete the questionnaires.
- Blood (about 1 tablespoon) and urine and/or feces (over 24 hours) will be collected to
check the status of the disease.
- Blood (about 1 tablespoon) will be drawn for genetic testing.
- Blood (about 1 tablespoon) will be drawn for routine tests. If you are able to become
pregnant, a pregnancy test will also be performed.
- If your doctor thinks it is necessary, you will have a MRI or a CT scan, a liver
ultrasound, a fatty tissue biopsy, and/or a bone marrow aspiration or biopsy, to check
the status of the disease.
Long Term Follow-Up:
After the end-of-treatment visit, you will be contacted either by telephone or during one of
your standard of care office visits every 3 to 6 months and asked how you are doing. If you
are contacted by phone, the call will take about 5 minutes.
This is an investigational study. Pomalidomide, Melphalan, and Dexamethasone are FDA
approved and commercially available for the treatment of MM. The study drug combination is
not FDA approved or commercially available as a first-line treatment for AL amyloidosis. It
is currently being used for research purposes only.
Up to 54 patients will participate in this multicenter trial. Up to 42 will be enrolled at
MD Anderson.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD) of Pomalidomide with Melphalan and Dexamethasone (PMD).
Maximum tolerated dose defined as highest dose level at which less than 33% of patients experienced dose-limiting toxicities. Dose-limiting toxicities defined as (grade 4 neutropenia lasting more than 7 days despite G-CSF administration, any other grade 4 hematologic toxicity, any grade 3 non-hematologic toxicity, or a new cycle delay beyond a maximum of 4 weeks) in less than 33% of patients during the first cycle of therapy.
28 days
Yes
Robert Orlowski, MD, PHD
Principal Investigator
UT MD Anderson Cancer Center
United States: Food and Drug Administration
2012-0215
NCT01807286
July 2013
Name | Location |
---|---|
UT MD Anderson Cancer Center | Houston, Texas 77030 |
Tufts Medical Center | Boston, Massachusetts 02111 |