RAD001 Study in Treatment of Relapsed or Refractory Acute Lymphocytic Leukemia

Leukemia Clinical Trial

Official title: Phase I/II Study of Hyper-CVAD Plus RAD001 (Everolimus) for Patients With Relapsed or Refractory Acute Lymphocytic Leukemia (ALL)

Status Completed

Clinical Trial Summary

The goal of Phase I of this clinical research study is to find the highest tolerable dose of RAD001 (everolimus) when given in combination with the standard chemotherapy regimens to patients with ALL.

The goal of Phase II of this study is to learn if the drug combinations can help to control ALL. The safety of these drug combinations will be also studied in both phases.

Clinical Trial Description

The Study Drugs:

Everolimus is designed to stop cancer cells from multiplying. It may also stop the growth of new blood vessels that help tumor growth, which may cause the tumor cells to die.

You will receive everolimus with 2 different chemotherapy combinations during alternating cycles. This means that you will receive 1 combination on Cycles 1, 3, 5, and 7 and the other combination during Cycles 2, 4, 6, and 8.

The first chemotherapy regimen is called hyper-CVAD. Hyper-CVAD includes cyclophosphamide, vincristine, Adriamycin (doxorubicin), and dexamethasone. This combination is designed to kill leukemia cells.

The other chemotherapy regimen includes the drugs methotrexate and ara-C (cytarabine). This combination is also designed to kill leukemia cells.

Study Groups and Everolimus Dose Levels:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 3 groups of 3-6 participants will be enrolled in the Phase I portion of the study, and up to 30 participants will be enrolled in Phase II.

If you are enrolled in the Phase I portion, the dose of everolimus you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of everolimus. Each new group will receive a higher dose of everolimus than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of everolimus is found.

If you are enrolled in Phase II, you will receive everolimus at the highest dose that was tolerated in the Phase I portion.

In this study, everolimus is the only study drug where different dose levels are being tested and compared. All other drugs will be given at the same dose level.

Central Venous Catheter (CVC):

If you do not already have a CVC, you will have a CVC placed. A CVC is a plastic tube usually placed under the collarbone. You will sign a separate consent for this procedure. Some of the study drugs will be given through the CVC.

Everolimus Administration:

During all cycles, you will take everolimus once a day followed by a big glass of water. The tablets must not be chewed, broken or crushed. You may either take everolimus on an empty stomach or after a low fat meal. Taking everolimus after large, fatty meals is not advised because it will lower the amount of everolimus your body absorbs. Some examples of a low fat meal include: cereal with fat free milk, muffin/bagel with fat free spread, fruit salad, and so on. Always follow the instructions for use of everolimus given to you by your study doctor. Your first dose of everolimus will occur 1 day before you begin receiving chemotherapy.

Do not miss any tablets/capsules. You should take everolimus about the same time each day preferably in the morning.

If your study doctor thinks it is needed or if you experience severe side effects, everolimus may be stopped and then started again with a lower dose or may be stopped completely.

Chemotherapy Administration:

Each cycle will last about 21 days. The timing of each new cycle will depend on when your blood counts recover.

Cycles 1, 3, 5, and 7:

During Cycles 1, 3, 5, and 7, you will receive hyper-CVAD. The drugs will be given at the following times:

• On Days 1-3, you will receive cyclophosphamide by vein over 2-3 hours every 12 hours.

• On Days 1-4 and 11-14, you will receive dexamethasone by mouth or by vein. If by vein, the infusion will take a few seconds.

• On Day 4, you will receive doxorubicin over 24 hours through a CVC.

• On Days 4 and 11, you will receive vincristine by vein over 2-3 hours.

Cycles 2, 4, 6, and 8:

During Cycles 2, 4, 6, and 8, you will receive the methotrexate and cytarabine by vein as follows:

• On Day 1, you will receive methotrexate by vein over 24 hours.

• On Day 1, you may receive leucovorin (citrovorum) by vein (over 15 minutes) for 2-3 days. Leucovorin is given to help prevent methotrexate side effects.

• On Days 2-3, you will receive cytarabine by vein over 2 hours every 12 hours.

• On Days 1-3, you will receive methylprednisone over 2 hours every 12 hours for 6 doses.

Cycles 1-8:

You will also receive either Neupogen (filgrastim) or pegfilgrastim to help your bone marrow recover from chemotherapy. Filgrastim or pegfilgrastim will be injected under the skin within 72 hours after each cycle of chemotherapy. If you receive filgrastim, it will be given daily until your counts recover. If you receive pegfilgrastim, it will be given 1 time.

You will also receive small doses of methotrexate and Ara-C, one after the other, by a spinal tap to help prevent the disease from coming back in the fluid surrounding your brain during each cycle. During a spinal tap, a doctor or technician inserts a needle through the skin and the soft tissues of the lower back to reach a pocket of fluid that is part of the fluid space that surrounds the brain and the spinal cord. Once the fluid space is reached, chemotherapy drugs can be administered. The procedure is done under local anesthesia. An Ommaya reservoir (which holds the drugs being given) may also be implanted surgically if you have difficulty with the spinal treatments. An Ommaya reservoir is a tube inserted under the skin of the scalp that enters into the spinal fluid cavity of the brain. You will be asked to sign a separate consent form for this procedure. The number of doses you receive will depend on how many doses the study doctor thinks are needed. If you start with leukemia in the brain, it will be given 2 times a week until there is no leukemia present and then 1 time a week for 4 weeks. Sometimes, a sample of the spinal fluid collected from the spinal taps may be tested to look for leukemia cells.

Maintenance Chemotherapy:

After you have completed 8 cycles, you will begin monthly (about every 28 days, depending on your blood cell count recovery) maintenance chemotherapy for about the next 24 months. You will take the following drugs:

• You will take 6-mercaptopurine by mouth with water every day.

• You will receive methotrexate by vein (over 2 hours) or mouth every week.

• You will receive vincristine by vein over 30 minutes every 28 days.

• You will take prednisone by mouth for 5 days every month.

Study Visits:

During Cycle 1, blood (about 1 tablespoon) will be drawn for routine tests 1-3 times every week. During Cycles 2-8, blood (about 1 tablespoon) will be drawn for routine tests every 1-4 weeks.

During Cycles 1 and 2, you will have physical exam every week. After Cycle 2, you will have a physical exam every 3-4 weeks.

At Weeks 2 and 3 of Cycle 1, you will have a bone marrow aspirate to check for response. Depending on the results of the sample, this will be repeated every 1-2 weeks.

At Week 4-6 of Cycle 1, you will have a chest x-ray.

After Cycle 2 is over, the following tests and procedures will be performed:

• You will have a physical exam.

• Blood (about 8 teaspoons) and urine will be collected for routine tests.

• You will have a bone marrow aspirate.

• You will have a chest X-ray or computed tomography (CT) scan if needed.

If you had a positive hepatitis B test at screening, every month, blood (about 1 tablespoon) will be drawn to test the level of hepatitis B virus in your blood.

If your have risk factors and/or a positive Hepatitis C test results at screening, every month, blood (about 1 tablespoon) will be drawn to test the level of Hepatitis C virus in your blood.

Length of Study:

You may receive up to 32 cycles of study drugs. You will be taken off study early if the disease gets worse, your doctor decides it is in your best interest to stop, or you have intolerable side effects.

End-of-Study Visit:

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

• You will have a physical exam.

• Blood (about 8 teaspoons) will be drawn for routine tests.

• You will have a bone marrow aspirate.

• If your doctor thinks it is needed, you will have a chest x-ray or CT scan.

Follow-up Visits:

You will have follow-up visits every 3 to 6 months. At these visits, the following tests and procedures will be performed:

• You will have a physical exam.

• You will have a bone marrow aspirate.

• Blood (about 3 teaspoons) will be drawn for routine tests.

• If your doctor thinks it is needed, you will have a chest x-ray.

This is an investigational study. All the chemotherapy drugs used on this study are FDA approved and commercially available for treating ALL. Everolimus is FDA approved and commercially available for the treatment of certain types of breast cancer. At this time, the combination is only being used in research.

Up to 42 patients will take part in this study. All will be enrolled at MD Anderson. ;

Related Conditions & MeSH terms

• Acute Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

• NCT number: NCT00968253
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 2009
• Completion date: December 2015