Last updated on September 2018

Hyper-CVAD Regimen in Sequential Combination With Blinatumomab as Frontline Therapy for Adults With B-Cell Lineage Acute Lymphocytic Leukemia


Brief description of study

The goal of this clinical research study is to learn if Blinacyto (blinatumomab), when given after Hyper-CVAD, can help to control newly diagnosed B-Cell Lineage ALL. The safety of this drug will also be studied.

This is an investigational study. Blinatumomab is FDA approved and commercially available for the treatment of ALL that has been treated before or has come back. It is investigational to use the drug as a first option for the treatment of the disease. Hyper-CVAD is FDA approved and commercially available for the treatment of ALL. The study doctor can explain how the study drugs are designed to work.

Up to 60 participants will be enrolled in this study. All will take part at MD Anderson.

Detailed Study Description

Study Drug Administration:

Study Cycles 1-4 are about 3 weeks each. Study Cycles 5-8 are about 6 weeks each.

If you are found to be eligible to take part in this study, you will receive a CVC if you do not already have one. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure.

Hyper-CVAD (Cycles 1 and 3):

During Cycles 1 and 3 you will also receive the following drugs:

  • On Days 1-3, you will receive cyclophosphamide 2 times each day (about 12 hours apart) by vein over about 3 hours.
  • On Days 1-3, you will receive mesna by vein non-stop to help prevent side effects. The mesna infusion will start about one hour prior and end about 12 hours after the last dose of cyclophosphamide.
  • On Days 1-4 and 11-14, you will receive dexamethasone 1 time a day by mouth or by vein over 30 minutes.
  • On Days 1 and 11, if your doctor thinks it is in your best interest, you may receive ofatumumab or rituximab by vein over about 4 to 6 hours. The study doctor will decide how long the infusion will last. If you receive ofatumumab, you will also receive a dose on Day 2 of Cycle 1.
  • On Day 2, you will receive methotrexate by lumbar puncture.
  • On Day 4, you will receive doxorubicin by vein non-stop for 1 day through the CVC.
  • On Days 4 and 11, you will receive vincristine by vein over about 15 minutes.
  • On Day 7, you will receive cytarabine by lumbar puncture.

During Cycles 2 and 4, you will also receive the following drugs:

  • On Day 1, you will receive methotrexate by vein over about 24 hours.
  • On Days 1 and 8, if your doctor thinks it is in your best interest, you may receive ofatumumab or rituximab by vein over about 4 to 6 hours. The study doctor will decide how long the infusion will last.
  • On Days 2 and 3, you will receive cytarabine by vein 2 times each day (about 12 hours apart) over about 2 hours.
  • On Day 5, you will receive cytarabine by lumbar puncture.
  • On Day 8, you will receive methotrexate by lumbar puncture.

You may receive filgrastim or pegfilgrastim as an injection under the skin at the end of every cycle to help raise your blood cell counts.

If your doctor thinks it is needed to help reduce the risk of side effects, you may receive leucovorin by vein 4 times a day for about 8 doses, beginning about 12 hours after the methotrexate dose ends.

You may be given other drugs to help prevent side effects. The study staff will tell you about these drugs, how they will be given, and the possible risks.

After you have finished receiving Hyper-CVAD, you will receive blinatumomab nonstop for Weeks 1-4 every 6 weeks of Cycles 5-8. If your doctor thinks it is in your best interest, he may choose to begin blinatumomab earlier than Cycle 5.

You will receive blinatumomab through a peripherally inserted central catheter. This allows you to receive the drug constantly over a long period of time. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure.

During the first cycle of blinatumomab, the infusion will be started in the hospital. You will be in the hospital for up to 9 nights of Cycle 1 and Days 1 and 2 of Cycle 2 so that you can be monitored for side effects. Your doctor will decide when you can leave the hospital.

Blinatumomab will be delivered by a small pump, which you will carry with you for the whole time you receive the drug. You will be given a shoulder or belt bag to hold the pump and infusion bag. You will be able to wear regular clothes, walk around, and perform daily living activities. You will be given instructions for taking a shower and other activities. However, because the line must be kept free of infection and connected to the pump, there will be some things that you should not do, such as go swimming. The study staff will give you more information on activities you should not do while receiving the drug.

You will need to come to MD Anderson to have the infusion bags changed about every 48 hours. The study staff will let you know if you need to return to the clinic.

You may be given a medication diary to record when you take your oral medications.

Maintenance Therapy:

After you have received 4 cycles of blinatumomab, you may be able to receive maintenance therapy. During Maintenance Therapy, you will receive the following drugs: you will receive a cycle of blimatumomab therapy after every 3 cycles of maintenance therapy with 6-mercaptopurine, methotrexate, vincristine and prednisone for a total of about 15 cycles.

Study Cycles 1-3, 5-7, 9-11, 13-15 are about 4 weeks each. During these cycles, you will receive the following:

  • Every day, you will take 6-mercaptopurine by mouth 3 times a day.
  • Every week, you will take pills of methotrexate.
  • About every 4 weeks, you will receive vincristine by vein 1 time over about 15 minutes.
  • On Days 1-5 of every cycle, you will take prednisone by mouth.

Study Cycles 4,8,12 are about 6 weeks each. During these cycles, you will receive blimatumomab nonstop for Weeks 1-4 every 6 weeks.

Study Visits:

At the beginning of every cycle, you will have a physical exam.

One (1) time each week during Cycles 1-8, then every month during the Maintenance Phase, blood (about 2-3 tablespoons) will be drawn for routine tests.

On Day 21 (+/-3 days) of Cycle 1 and after you finish receiving Hyper CVAD and/or before you begin receiving blimatumomab, blood (about 2 teaspoons) will be drawn to check the status of the disease. This will then be done every week until the disease appears to go away.

On Days 14 (+/- 3 days) and 21 (+/- 3 days) of Cycle 1, you will have a bone marrow biopsy and/or aspiration to check the status of the disease. This will then be done every week and every month during Hyper-CVAD and blinatumomab until the disease appears to go away. If the disease appears to completely go away, you may need to have another bone marrow biopsy/aspiration at the time after you finish receiving Hyper-CVAD and/or before you begin receiving blinatumomab.

Within about 14 days before you receive blinatumomab, you will have a neurological exam.

If the disease does not appear to have completely gone away, on Days 42 (+/- 7 days) of Cycle 5, you will have a bone marrow biopsy/aspiration to check the status of the disease. This will then be done after every cycle while you receive blinatumomab, and then every 4 months after that.

If the disease does appear to have completely gone away, you will have a bone marrow biopsy/aspiration prior to start Cycle 7 and before you start Maintenance Therapy and then every 4 months during Maintenance Therapy.

At any point that the doctor thinks it is needed, you will have a PET-CT scan or x-ray to check the status of the disease.

At any point within 60 days after your treatment is started, you will have a cheek swab if this has not been completed before the time your treatment has started.

Length of Study:

You will receive up to 4 cycles of intensive chemotherapy and up to 4 cycles of blinatumomab, followed by about 15 cycles of maintenance therapy. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Follow -Up:

About 30 days after your last dose of study drugs, you may be called by a member of the study team and asked about how you are feeling and about any side effects you may be experiencing. This call should last about 5-10 minutes.

Long-Term Follow-Up:

After you have received your last dose of study drugs, you will be called by a member of the study team periodically. You will be asked how you are feeling. The phone call should last about 5-10 minutes.

Clinical Study Identifier: NCT02877303

Contact Investigators or Research Sites near you

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Elias Jabbour, MD

University of Texas MD Anderson Cancer Center
Houston, TX United States
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