Pomalidomide With Melphalan and Dexamethasone for Untreated Systemic AL Amyloidosis

Myeloma Clinical Trial

Official title: A Phase I/II Clinical Trial of Pomalidomide With Melphalan and Dexamethasone in Patients With Newly Diagnosed Untreated Systemic AL Amyloidosis: Trial Stopped During Phase I

Status Terminated

Clinical Trial Summary

The goal of this clinical research study is to find the highest tolerable dose of pomalidomide that can be given in combination with melphalan and dexamethasone that can be given to patients with AL amyloidosis. The safety of this drug combination will also be studied.

Pomalidomide is designed to change the body's immune system. It may also interfere with the development of tiny blood vessels that help support tumor growth. This may decrease the growth of cancer cells.

Melphalan is designed to damage the DNA (genetic material) of cells, which may cause cancer cells to die.

Dexamethasone is a corticosteroid that is similar to a natural hormone made by your body. Dexamethasone is often given to Multiple Myeloma (MM) patients in combination with other chemotherapy to treat cancer.

Planned Phase I/II Study terminated early during Phase I portion without continuation to Phase II.

Clinical Trial Description

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.

After 2 cycles of therapy, you may be referred to a transplant specialist, if you are eligible for a stem cell transplant.

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.

You will also be given a study drug diary. Each time you take pomalidomide, melphalan or dexamethasone 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.

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, melphalan, or dexamethasone 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 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 routine tests. If you are able to become pregnant, a pregnancy test will also be performed.

• If your doctor thinks it is needed, you will have an EKG and an ECHO.

On Days 8 and 22 of Cycle 1:

• Blood (about 1 tablespoon) will be drawn for routine tests.

• If you are able to become pregnant, blood (about 2 teaspoons) will be drawn for a pregnancy test.

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.

• Blood (about 1 tablespoon) will be drawn for routine tests.

• If you are able to become pregnant, blood (about 2 teaspoons) will be drawn for a pregnancy test.

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.

I-f your doctor thinks it is needed, 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.

• Urine will be collected for routine tests.

• If your doctor thinks it is needed, you will have a bone marrow aspiration and biopsy to check the status of your disease and for genetic testing.

• If your doctor thinks it is needed, you will have an EKG and an ECHO.

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.

• If you are able to become pregnant, blood (about 2 teaspoons) will be drawn for a pregnancy test.

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 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.

• If your doctor thinks it is needed,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 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.

• Urine will be collected for routine tests.

• If your doctor thinks it is needed, you will have an EKG and an ECHO.

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.

• If your doctor thinks it is needed, 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.

• Urine will be collected for routine tests.

• If your doctor thinks it is needed, you will have an EKG and an ECHO.

On Day 15 of Cycles 1 and beyond:

-If you are able to become pregnant, blood (about 2 teaspoons) will be drawn for a pregnancy test.

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 30 days 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.

• You will have an ECHO.

• 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) will be drawn 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 28 days after your last dose of pomalidomide if you have regular periods or 14 and 28 days after your last dose of pomalidomide if you have irregular periods.

• If your doctor thinks it is necessary, you will have a MRI or a CT scan to check the status of the disease.

• If the doctor thinks it is possible, you will have a bone marrow aspiration and biopsy to check the status of disease and for genetic testing.

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 be enrolled at The University of Texas (UT) MD Anderson. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyloidosis
• Myeloma

• NCT number: NCT01807286
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Terminated
• Phase: Phase 1
• Start date: January 2014
• Completion date: February 2016