Clinical trial NCT01531998
Conditions: Myeloma
Keywords: Myeloma Multiple Myeloma MM Newly diagnosed Lenalidomide CC-5013 Revlimid Bortezomib Velcade LDP-341 MLN341 PS-341 Siltuximab CNTO 328 Anti-IL-6 Antibody Dexamethasone Decadron M. D. Anderson Symptom Inventory Module MDASI-MM Questionnaires Surveys
Sponsor: M.D. Anderson Cancer Center
Start date: 2012-05-01; Completion date: 2014-05-01
Enrollment: 14 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of this clinical research study is to find the highest tolerable dose of Siltuximab that can be given in combination with Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone to patients with MM. The safety of this drug combination will also be studied.

Detailed description:
The Study Drugs:

Siltuximab is designed to block IL-6, which is a protein that plays an important role in the survival of myeloma cancer cells. This may slow the growth of cancer cells or cause the cancer cells to die.

Bortezomib is designed to block a protein that plays a role in cell function and growth. This may cause cancer cells to die.

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

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

Study Groups:

If you are found to be eligible to take part in this study, based on when you join the study you will be enrolled in the Phase I or Phase II portion. If you are in Phase I, you will be assigned to a dose level of Siltuximab based on when you join this study. Up to 2 dose levels of Siltuximab will be tested. Three (3) to 6 participants will be enrolled at each dose level. The first group of participants will receive the highest dose level. If intolerable side effects are seen in the first group, the next group will receive a lower dose.

All participants will receive the same dose level of bortezomib, lenalidomide, and dexamethasone.

After the highest tolerable dose level is found, up to an extra 54 participants will receive the study drugs at this dose level in the Phase II part of the study.

Study Drug Administration:

Induction Therapy - Each cycle is 21 days. On Days 1, 4, 8, and 11 of Cycle 1 up to Cycle 8 (induction therapy), you will receive bortezomib through a needle under the skin or by vein over 3-5 seconds.

On Days 1-14 of every cycle, you will take lenalidomide by mouth 1 time each day. Swallow lenalidomide capsules whole with 1 cup (about 8 ounces) of water. Do not break, chew, or open the capsules.

On Day 1 of every cycle, you will receive Siltuximab by vein over 1 hour.

On Days 1, 2, 4, 5, 8, 9, 11, and 12 of Cycles 1-8 (induction therapy), you will take dexamethasone by mouth 1 time a day. After 8 cycles, you may continue to take dexamethasone if the doctor thinks it is needed. Dexamethasone should be taken with food.

You can take the study drugs any time during the day but you should take them at the same time every day.

If you miss a dose of lenalidomide, 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). If you take more than the prescribed dose of lenalidomide, you should seek emergency medical care if needed and contact the study staff right away.

You will be given a study drug dosing calendar for each cycle to record the lenalidomide and dexamethasone you will be taking at home. Please bring the dosing calendar and pill bottles to your study visit at the beginning of each new cycle.

If the doctor thinks it is in your best interest, you may have a stem cell transplant anytime after 4 cycles of induction therapy You will sign a separate consent form that will describe the procedure and the risks in detail.

Maintenance Phase - Each cycle is 28 days. If you want to delay the stem cell transplant, after 4-8 cycles, you will begin the maintenance phase.

During the maintenance phase:

* You will take lenalidomide on Days 1-21 of each cycle.
* You will take dexamethasone by mouth once a week.
* You will receive Siltuximab by vein on Day 1 of every cycle.

Study Visits:

On Day 1 of Cycle 1:

* You will have a physical exam, including measurement of your height, weight and vital signs.
* Your medical history will be updated.
* You will be asked to list any drugs you may be taking and if you have had any side effects.
* Your performance status will be recorded.
* You will have an ECG.
* You will complete 2 questionnaires about your day-to-day activities and quality of life. They should take about 5 minutes each to complete.
* If you are able to become pregnant, you will have a blood or urine (about 1 teaspoon) pregnancy test.
* Blood (about 2 tablespoons) will be drawn to measure protein levels, which may help researchers learn more about how to better treat myeloma.

On Day 1 of Cycles 2-8:

* You will have a physical exam, including measurement of your height, weight and vital signs.
* Your performance status will be recorded.
* You will be asked to list any drugs you may be taking and if you have had any side effects.
* Blood (about 5 tablespoons) will be drawn for routine tests.
* Blood (about 1 teaspoon) and/or urine will be collected to check the status of the disease. If urine is collected, you will collect the urine over 24 hours. You will be provided with a container to collect the urine in.
* Blood (about 2 tablespoons) will be drawn to measure protein levels, which may help researchers learn more about how to better treat myeloma.
* You will complete the questionnaire about your day-to-day activities
* If you are able to become pregnant, you will have a blood or urine (about 1 teaspoon) pregnancy test.

On Days 4 of Cycles 1-8:

-Blood (about 4 tablespoons) will be drawn for routine tests.

On Day 8 of Cycle 1:

-You will have a bone marrow aspirate to better understand how the drugs are affecting the myeloma. To collect a bone marrow aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

On Days 8 of Cycles 1-8:

-Blood (about 4 tablespoons) will be drawn for routine tests. During Cycle 1, this routine blood draw will include a pregnancy test if you are able to become pregnant.

On Day 11 of Cycles 1-8:

-Blood (about 4 tablespoons) will be drawn for routine tests.

At the end of induction therapy (or if you are going to have a stem cell transplant, at the end of Cycle 4):

* You will have a physical exam.
* You will be asked to list any drugs you may be taking and if you have had any side effects.
* Blood (about 5 tablespoons) and urine will be collected for routine tests.
* You will have a skeletal survey to check the status of the disease.
* If the disease completely responds to the study drugs, you will have a bone marrow aspiration and/or biopsy to check the status of the response.

On Day 1 of Cycles 9 and beyond (Maintenance Therapy):

* You will have a physical exam, including measurement of your vital signs, height, and weight.
* Your performance status will be recorded.
* You will be asked to list any drugs you may be taking and if you have had any side effects.
* Blood (about 4 tablespoons) will be drawn for routine tests.
* Blood (about 1 teaspoon) and/or urine will be collected to check the status of the disease. If urine is collected, you will collect the urine for 24 hours. You will be provided with a container to collect the urine in.
* If the doctor thinks it is needed, you will have a skeletal survey to check the status of the disease.
* If the doctor thinks it is needed, you will have an MRI scan or CT scan to check the status of the disease.
* Blood (about 2 tablespoons) will be drawn to measure protein levels, which may help researchers learn more about how to better treat myeloma.
* You will complete the questionnaires about your day-to-day activities and quality of life.

Pregnancy Tests:

During induction therapy, if you are a woman who is able to become pregnant and you have regular or no periods, you will have a blood (about 1 tablespoon) or urine pregnancy test weekly for the first 21 days and then every 21 days while on therapy (including breaks in therapy). If you are a woman who is able to become pregnant and your cycles are irregular, you will have a blood (about 1 tablespoon) or urine pregnancy test weekly for the first 21 days during then every 11-14 days while on therapy (including breaks in therapy).

During maintenance therapy, if you are a woman who is able to become pregnant and have regular or no menstruation, you must have a pregnancy test every 28 days while on therapy (including breaks in therapy). If you are a woman who is able to become pregnant and your cycles are irregular, you will have a blood (about 1 tablespoon) or urine pregnancy test every 14 days (+/-1 day) and every 28 days.

Length of Study:

You may stay on study for as long as the disease does not get worse, you have not experienced intolerable side effects, and if the study doctor thinks it is in your best interest.

End-of-Treatment Visit:

Within 1 month after the last dose of study drugs, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

* Your performance status will be recorded.
* You will be asked to list any drugs you may be taking and if you have had any side effects.
* You will have a physical exam, including measurement of your height and weight.
* You will have a skeletal survey.
* You will have a bone marrow biopsy to check the status of the disease.
* Blood (about 4 tablespoon) and urine will be collected for routine tests.

Long-Term Follow-Up:

If you go off study for reasons other then the disease getting worse, blood (about 5 tablespoons) will be drawn for routine tests. This will done every 3 months for the first 2 years, every 6 months for Years 3 and 4, and yearly for Years 5 and 6. The long term visits will be to check disease status, survival, long term side effects, and secondary cancers.

This is an investigational study. Siltuximab is not FDA approved or commercially available. It is only being used for research at this time. Bortezomib is FDA approved and commercially available for the front-line treatment of MM. Lenalidomide is FDA approved and commercially available for the treatment of certain types of myelodysplastic syndrome and for use with dexamethasone for patients with MM who have received at least 1 therapy. The use of this drug combination to treat MM is investigational.

Up to 11 patients will take part in this study. All will be enrolled at MD Anderson.

Arms: arm 1: Induction: Lenalidomide 25 mg orally Days 1-14; Bortezomib 1.3 mg/m2 intravenous Days 1, 4, 8 and 11; Dexamethasone 20 mg orally Days 1, 2, 4, 5, 8, 9, 11, 12. Siltuximab 11 mg/kg intravenous Day 1.

If delayed transplant, induction therapy continued up to 2 cycles beyond achieving a CR/nCR (minimum of 4 cycles of therapy and a maximum of 8 cycles of therapy) and then transition to maintenance regimen described below.

Maintenance therapy: Lenalidomide at last tolerated dose Day 1-21 every 28 days for up to 12 months and then may be reduced to 10 mg.

Siltuximab 11 mg/kg intravenous every 21 days, or maximum tolerated dose from induction therapy. Bortezomib at last tolerated dose Day 1 and Day 8 Dexamethasone at last tolerated dose or 20 mg weekly.
Interventions: intervention 1: Lenalidomide intervention 2: Bortezomib intervention 3: Siltuximab intervention 4: Dexamethasone intervention 5: Questionnaires
Intervention descriptions: intervention 1: Induction Phase: 25 mg by mouth daily on Days 1-14. Maintenance Phase: at last tolerated dose from Induction Phase day 1-21 every 28 days for up to 12 months and then may be reduced to 10 mg. intervention 2: Induction Phase: 1.3 mg/m2 by vein daily on Days 1, 4, 8 and 11.

Maintenance Phase: 1.3 mg/m2 by vein or last tolerated dose on Day 1 and Day 8. intervention 3: Induction Phase Starting Dose: 11 mg/kg by vein on Day 1.

Maintenance Phase: 11 mg/kg intravenous every 21 days, or maximum tolerated dose from induction therapy. intervention 4: Induction Phase: 20 mg by mouth on Days 1, 2, 4, 5, 8, 9, 11, 12.

Maintenance Phase: 20 mg by mouth on Days 1, 2, 4, 5, 8, 9, 11, 12. If participant still on Dexamethasone, when entering Maintenance Phase, dose reduced to 20 mg a week. intervention 5: M. D. Anderson Symptom Inventory Module (MDASI-MM) completed Day 1, Day 8 of Cycle 1 - 8, and on Day 1 of Cycle 9 and beyond.

Protocol documents: