Cyclophosphamide and Fludarabine to Treat Lupus Nephritis
Status:
Completed
Trial end date:
2002-11-01
Target enrollment:
Participant gender:
Summary
This study will test the safety and effectiveness of combination therapy with
cyclophosphamide (Cytoxan) and fludarabine in treating lupus nephritis (kidney inflammation).
This condition, common in patients with systemic lupus erythematosus, is caused by abnormal
action of immune cells called lymphocytes against the kidneys. Left untreated, severe cases
can result in loss of kidney function. The current treatment of choice-intermittent high
doses (pulses) of cyclophosphamide-does not work in all patients and causes infertility in
many women. The rate of infertility in men is not known. This study will examine whether
fludarabine can safely be given with significantly lower doses of cyclophosphamide, and if
this combination controls kidney inflammation.
Patients 18 years of age and older with severe lupus nephritis (called proliferative lupus
nephritis) may be eligible for this study. Candidates will have a history and physical
examination; blood and urine tests; chest X-ray; electrocardiogram; cancer screening that may
include a Pap smear, mammogram, rectal examination, PSA testing, and sigmoidoscopy.
Participants will be divided into one of the following treatment groups:
Group 1-Patients undergo three treatment cycles of cyclophosphamide, taken by mouth, and
fludarabine, injected subcutaneously (under the skin). Patients receive both drugs on day 1
of the cycle, and fludarabine alone on days 2 and 3. This regimen is repeated once every 5
weeks for three cycles.
Group 2-Same as for Group 1, except fludarabine injections are given intravenously (through a
vein) for the second treatment cycle. Patients in this group have frequent blood sampling
during the first and second treatment cycles to monitor blood levels of the drug. Samples are
collected before the first injection is given and at 0.5, 1, 1.5, 2, 4, 8, 24 and 48 hours
after the third injection. A total 12 tablespoons of blood is drawn over a 2-month period.
All patients will have blood drawn once or twice a week during the first two cycles and then
less frequently to monitor blood counts. Some patients will have the following additional
procedures to test the effects of treatment on lymphocytes:
1. Blood sample collection
2. Bone marrow aspiration-The skin over the hip bone is cleaned and a local anesthetic is
injected into the outer covering of the bone. Bone marrow is suctioned through the
needle into an attached syringe. The procedure is done before treatment begins, at the
end of treatment, and 6 months after treatment.
3. Tonsillar biopsy-The tonsils are numbed with a local anesthetic and 1 to 4 pieces of
tissue are removed using special forceps. The procedure is done before treatment begins,
at the end of treatment, and 6 months after treatment.
4. Magnetic resonance imaging (MRI) of the abdomen-The patients lies on a table in a narrow
cylinder (the MRI scanner) containing a strong magnetic field, which is used to create
images of parts of the body in small section views.
Patients will be followed for at least 24 months to monitor late side effects and the
response to treatment.
Phase:
Phase 1
Details
Lead Sponsor:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)