A Phase II Study of Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR) in High-Risk Previously Untreated Patients With CLL
Fludarabine is a chemotherapy drug that is approved for the treatment of patients with
Chronic Lymphocytic Leukemia (CLL). Cyclophosphamide is also a chemotherapy drug that is
commonly used to treat patients with CLL. Rituximab and alemtuzumab are special proteins
(antibodies) that specifically target and attach to proteins on leukemia cells. These
targeted proteins may also be present on normal blood cells. When these antibodies bind to
the proteins on leukemia cells, they may help to stop or slow the growth of the disease.
The combination of fludarabine, cyclophosphamide, and rituximab has been used in the
treatment of previously untreated patients with CLL. The purpose of this study is to see if
there is added benefit with the addition of alemtuzumab to this combination.
Before you can start treatment on this study, you will have what are called "screening
tests." These tests will help the doctor decide if you are eligible to take part in the
study. You will have a complete physical exam, including routine blood tests (about 3
tablespoons). You may have either a chest x-ray or a computerized tomography (CT) scan if
your doctor thinks it is necessary. If you have not had a bone marrow biopsy collected in
the past 4 months, you will have a bone marrow sample collected at this time. To collect a
bone marrow biopsy, an area of the hip or chest bone is numbed with anaesthetic, and a small
amount of bone marrow is withdrawn through a large needle. Women who are able to have
children must have a negative blood or urine pregnancy test.
If you are found to be eligible to take part in this study, you may begin treatment. During
this study, you will have up to 6 "cycles" of treatment. A cycle is made up of treatment
with the study drugs for 5 days in a row, then around 3 and a half weeks (23 days) of no
treatment with the study drugs. On Days 1, 3, and 5 of each cycle, you will receive
alemtuzumab through a needle in a vein. On Day 2 of each cycle you will receive rituximab
through a needle in a vein. Cyclophosphamide and fludarabine will be given separately on
Days 3, 4, and 5 of each cycle through a needle in a vein. In addition to the study drugs,
you may also be given premedication and fluids by vein to help decrease the risk of side
effects. The premedication may include steroids that are used to decrease the risk of side
effects from the alemtuzumab and rituximab. They will be given before each dose of the
alemtuzumab and rituximab. The infusions for each daily treatment visit should take less
than 6 hours. This treatment will be given on an outpatient basis. The combination
treatment will be repeated every 4 weeks (1 cycle) for a total of up to 6 cycles.
You will receive acetaminophen (Tylenol) by mouth and diphenhydramine hydrochloride
(Benadryl) by mouth or vein 30-60 minutes before each dose of rituximab and alemtuzumab.
You will also receive hydrocortisone (a steroid) by vein before the first dose of
alemtuzumab of each cycle. These drugs will be used to help decrease the risk of side
effects. If side effects occur during a treatment, the doses of the drugs may be adjusted
(up or down) until the symptoms are gone. Also, if you experience side effects during
treatment, you must stay in the clinic to be observed, for 2 hours after the drug is given.
During the treatment and for 2 months after completion of treatment, you will need to take
antibiotics to decrease the risk of developing infection.
Trimethoprim/sulfamethoxazole (Bactrim DS, SMX) is a sulfa-drug, and you will be given this
to decrease the risk of a type of pneumonia called PCP pneumonia. If you are allergic to
sulfa drugs, a similar antibiotic may be given. You will take Valtrex to decrease the risk
of potential virus reactivation, including herpes. If you are allergic to Valtrex, a
similar antibiotic may be given. You may receive an antibiotic called valganciclovir
(Valcyte) to decrease the risk of another virus called cytomegalovirus. You may also take
allopurinol for the first week of the first course of treatment. This will help decrease
the risk of kidney damage from rapid destruction of your leukemia cells.
During the Cycle 1 of treatment, you will have blood drawn (about 2 tablespoons) for routine
blood tests once a week. Then, these blood tests will be repeated before the start of each
additional cycle (every 4 weeks). You will also see your treating doctor and provide a
history and have a routine physical exam done before each cycle of treatment.
After 3 cycles of treatment, you will have a physical exam and routine blood tests (about 2
tablespoons). You may also have either an x-ray or a CT scan. You will have another bone
marrow sample collected. These tests will be used to see if the disease is responding to
treatment. If it is found that the disease is not responding to treatment after the first 3
cycles of therapy, you will be taken off the study, and your doctor will discuss other
treatment options with you. If it is found that the disease is responding to treatment,
another 3 cycles (12 weeks) of treatment will be given. During these additional 3 cycles of
therapy, you will have blood drawn (about 2 tablespoons) once a week for routine blood
After 6 cycles of treatment, you will have a physical exam, around 2 tablespoons of blood
drawn for routine blood tests, and a bone marrow aspirate and biopsy to determine if your
leukemia is in remission.
If your disease gets worse or you experience any intolerable side effects, you will be taken
off the study, and your doctor will discuss other treatment options with you.
Around 3-6 months after you receive your last treatment cycle, you will have a physical exam
and routine blood tests (about 2 tablespoons). After that, you will have a physical exam
and routine blood tests (about 2 tablespoons) every 6 months for the next 2 years. If the
leukemia has gone into remission, you will have a bone marrow aspirate and biopsy at 6
months, 1 year, and 2 years after your last treatment cycle, to make sure it stayed in
remission. If your disease returns or if you start a new therapy, you will not need to
return for these visits. However, you should inform the study doctor/staff that you are
receiving other treatment.
This is an investigational study. All of the drugs used in the study are FDA approved and
commercially available. Their use together in this study, however, is experimental. As many
as 60 patients will take part in the study. All will be enrolled at M.D. Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall Participant Response
Overall Response: Complete remission (CR), nodular partial remission (nPR), and partial remission (PR) rates (overall response) in high-risk, previously untreated patients with CLL treated with CFAR. National Cancer Institute - Working Group (NCI-WG) response criteria. CR defined as zero nodes, Liver/spleen not palpable, zero symptoms, polymorphonuclear leukocyte (PMN)>1,500/uL, Platelets >100,000uL, Hemoglobin (untransfused) >11.0g/dL, Lymphocytes <4,000/uL and Bone Marrow Aspirate biopsy <30% lymphocytes with no lymphocyte infiltrate; PR defined as nodes >/= 50% decrease,Liver/spleen >/= 50% decrease, symptoms not applicable, PMN >1,500/uL or >50% improvement from baseline, Platelets 100,000uL or >/=50% decrease improvement from baseline, Hemoglobin (untransfused) >11.0g/dL or >50% improvement from baseline, Lymphocytes >50% decrease and Bone Marrow Aspirate biopsy Not Applicable for PR; with nPR defined same as PR but with <30% lymphocytes with residual disease on biopsy.
Evaluated after 3 courses of 4 week therapy (12 weeks)
William G. Wierda, M.D., Ph.D.
M.D. Anderson Cancer Center
United States: Institutional Review Board
|The University of Texas M.D. Anderson Cancer Center||Houston, Texas|