The goal of this clinical research study is to compare chemotherapy given with rituximab to
chemotherapy followed by rituximab. The safety of both treatment schedules will be studied.
Laboratory tests of genetic changes in blood and bone marrow before and during the study will
also be monitored.
Rituximab is a monoclonal antibody that is designed to attach to leukemia cells and activate
a series of events that may cause the cancer cells to die.
Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic
material of cells). This may increase the likelihood of the cells dying.
Mitoxantrone is designed to stop cancer cells from making DNA, which may stop the cells from
making more 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
If you are found eligible to take part in this study, you will be randomly assigned (as in
the flip of a coin) to 1 of 2 study groups. Each group will receive 8 "cycles" of treatment.
One (1) cycle will last 28 days.
If you are in Group 1, you will receive the following drugs at the following times. Each
study cycle is 28 days:
- Rituximab will be given through a needle in the vein over about 90 minutes on Days 1 and
8 of the first course Cycle 1, and on Day 1 only of Cycles 2-5 of Fludarabine/
Mitoxantrone/ Dexamethasone (FND) treatment.
- Fludarabine will be given through a needle in the vein over about 15 minutes on Days 2-4
of each cycle.
- Mitoxantrone will be given through a needle in the vein over about 15 minutes on Day 2
of each cycle.
- You will take dexamethasone by mouth with water on Days 1-5 of each 28-day cycle (FND).
If you miss any doses of the study drugs, please contact the research staff for instructions.
You will not receive rituximab in Cycles 6-8. When the 8 cycles are finished, you will begin
receiving the drug interferon on Days 1-14 each month for 1 year. Dexamethasone will be given
on Days 1-3 every month for 1 year.
Patients in group 2 will receive fludarabine on Days 1-3, mitoxantrone on Day 1, and
dexamethasone on Days 1-5 of each 28-day cycle. When 8 cycles of treatment are finished,
patients will begin receiving the drug interferon on Days 1-14 each month for 1 year.
Dexamethasone will be given on Days 1-3 every month for 1 year. About 4 months after
interferon treatment starts, patients in group 2 will begin receiving rituximab once a month
for 6 months.
Other drugs may be given to help decrease the risk of or ease side effects. Treatment may be
delayed or stopped if side effects are severe.
Most of the drugs are given by vein. A catheter (a tube) will be placed in a vein to decrease
the number of needle sticks. Dexamethasone may be taken by mouth instead of given by vein.
Some patients in this study, with changes in certain genes will receive different
chemotherapy drugs than other patients in the study will. The patients will, like all the
other patients, receive rituximab and interferon. But instead of the FND chemotherapy
regimen, they will receive a sequence of three regimens, CHOD-Bleo, ESHAP, and NOPP. The
drugs in these regimens include: cyclophosphamide, doxorubicin, vincristine, bleomycin,
VP-16, Ara-C, cisplatin, mitoxantrone, procarbazine, and corticosteroids (prednisone,
During the study, patients will have blood tests every week. Complete exams will be given in
Cycles 2 and 4; patients will return to the clinic for these. Every 2 or 3 cycles, patients
will have a chest x-ray and CT scans of the abdomen and pelvis. Bone marrow samples will be
taken. Heart function tests (EKG) will be done as needed.
After the study ends, patients will return for checkups every 3 months in the first year,
every 4 months in years 2 and 3, and every 6 months in years 4 and 5. After that, checkups
will be needed once a year. Blood and bone marrow samples will be taken at these visits.
This is an investigational study. Rituximab is approved by FDA for commercial use. The other
drugs used in the study are also approved for commercial use. About 210 patients will take
part in the study. All will be enrolled at University of Texas MD Anderson Cancer Center
1. Previously untreated stage IV indolent B-cell lymphoma [Amendment May 2001:
eligibility restricted to follicular lymphoma]
2. Age <76