Phase II Study of the Hyper - CVAD Regimen in Combination With Ofatumumab as Frontline Therapy for Patients With CD-20 Positive Acute Lymphoblastic Leukemia
Ofatumumab is designed to bind to the surface of a type of white blood cells. This may
cause cancer cells that come from these white blood cells to die.
Central Venous Catheter (CVC):
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.
During Cycles 1-8, you will receive ofatumumab during Cycles 1, 2, 3, and 4. During Cycles
1, 3, 5, and 7, you also will receive cyclophosphamide, vincristine, doxorubicin, and
dexamethasone (hyper-CVAD). During Cycles 2, 4, 6, and 8, you will also receive
methotrexate and cytarabine.
After Cycles 1-8, you will receive up to 30 cycles of Maintenance therapy.
- During Cycles 1-5, 8-17, and 20-30, you will receive 6-mercaptopurine, methotrexate,
vincristine, and prednisone.
- During Cycles 6 and 18 (or Cycles 7 and 19), you will receive cyclophosphamide,
vincristine, doxorubicin, dexamethasone, and ofatumumab.
- During Cycles 7 and 19 (or Cycles 6 and 18), you will receive methotrexate and
First Phase of Treatment (Cycles 1-8):
Every 21 days is a study cycle.
You will receive ofatumumab by vein over 4-6 hours on Days 1 and 11 of Cycles 1 and 3 and on
Days 1 and 8 of Cycles 2 and 4.
During Cycles 1, 3, 5, and 7, you will also receive the following drugs:
- On Days 1-3, you will receive cyclophosphamide 2 times a day by vein over 3 hours.
- On Days 1-3, you will receive mesna by vein non-stop for the 3 days. The mesna
infusion will end about 12 hours after the last dose of cyclophosphamide.
- On Day 4, you will receive doxorubicin by vein non-stop for 1 day through the CVC.
- On Day 4, you will receive vincristine by vein over 15 minutes.
- On Days 1-4 and 11-14, you will receive dexamethasone 1 time a day by vein over 30
minutes or by mouth.
During Cycles 2, 4, 6, and 8, you will also receive the following drugs:
- On Day 1, you will receive methotrexate by vein over 24 hours. 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 8 doses, beginning 12 hours after the Day 1 methotrexate dose
- On Days 2 and 3, you will receive cytarabine by vein 2 times a day over 2 hours.
You may receive filgrastim or pegfilgrastim at the end of every cycle to help raise your
blood cell counts after you finish chemotherapy. If you receive filgrastim, it will be given
by a needle under your skin. If you receive pegfilgrastim, it will be given by a needle
under your skin.
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.
If you are previously untreated for cancer, you will receive the following drugs during
Cycles 1-4 to help prevent disease in your brain and spinal fluid:
- On Day 2, you will receive methotrexate as an injection into the spinal canal (the
space surrounding the spinal cord).
- On Day 7, you will receive cytarabine as an injection into the spinal canal.
If you have mediastinal lymphoblastic lymphoma and bulky mediastinal disease or mediastinal
lymphadenopathy (enlarged lymph nodes in the chest area), you may have radiation therapy to
the chest area based on the status of the disease. The radiation therapy will be given after
you recover from Cycle 8 and before you start Maintenance therapy. Your doctor will explain
radiation therapy to you in more detail, and you will be required to sign a separate consent
form for this procedure.
During Maintenance Cycles 1-5, 8-17, and 20-30:
- You will take 6-mercaptopurine by mouth 3 times daily.
- On Day 1, you will receive vincristine by vein over 15 minutes.
- You will take methotrexate by mouth weekly.
- On Days 1 and 5, you will take prednisone by mouth.
During Maintenance Cycles 6 and 18 (or Cycles 7 and 19), you will receive the same drugs on
the same schedule as you did during Cycles 1-8.
During Maintenance Cycles 7 and 19 (or Cycles 6 and 18):
- You will take methotrexate by mouth weekly.
- You will receive pegylated asparaginase on Day 2 by vein over 2 hours
If you have Burkitt Leukemia, you will only receive induction, consolidation and intrathecal
chemotherapy (injected into the spinal canal). You will not receive maintenance therapy.
You will have a physical exam before each cycle.
One (1) time a week during Cycles 1-8, then 1 time a month during Maintenance, blood (about
2-3 teaspoons) will be drawn for routine tests.
On Day 14 of Cycle 1, then 1 time a week, you will have a bone marrow aspiration and/or
biopsy to check the status of the disease. If the cancer goes into remission (no sign of
disease) the bone marrow aspirations/biopsies will then be performed every 4 months.
You will have a chest x-ray or PET/CT scan anytime the doctor thinks it is needed.
Length of Study:
You may receive up to 38 cycles of study drugs. You will no longer be able to take the
study drugs if the disease gets worse, if intolerable side effects occur, or if you are
unable to follow study directions.
You will be followed for side effects until 30 days after your last dose of study drugs.
You will have blood (about 2-3 teaspoons) drawn.
The study staff will call you every 3 months for 1 year after you finish receiving the study
drugs. During the calls, you will be asked how are you feeling and about any side effects
you may have had and any drugs you may have taken.
This is an investigational study. Ofatumumab is FDA approved or commercially available for
the treatment of chronic lymphocytic leukemia. Its use to treat ALL is investigational.
Up to 80 patients will take part in this study. All will be enrolled at MD Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Event-Free Survival (EFS)
Event-free survival measured from the start of therapy until failure to respond, relapse or death.
Assessed beginning Day 14 of Cycle 1, on-going to disease progression (estimated 3+ years)
Elias Jabbour, MD
UT MD Anderson Cancer Center
United States: Food and Drug Administration
|UT MD Anderson Cancer Center||Houston, Texas 77030|