This study will examine the safety and effectiveness of the drug Rituximab in treating
hepatitis C-associated cryoglobulinemic vasculitis. About 5 percent of patients with
hepatitis C develop cryoglobulinemic vasculitis. This syndrome, characterized by
inflammation of blood vessels (vasculitis), may involve the skin, joints, kidneys, nerves
and other sites, and cause skin rashes, joint pain, weakness, fatigue, and numbness. About
10 to 30 percent of patients develop kidney disease, which, in some cases, can lead to
Although the cause of cryoglobulinemic vasculitis is not known, a critical component is the
presence of cryoglobulins-abnormal proteins that white blood cells called B lymphocytes
produce in response to the chronic hepatitis C infection. Rituximab decreases the number of
B cells. The Food and Drug Administration approved Rituximab in 1997 for the treatment of
B-cell non-Hodgkin's lymphoma.
Patients between 18 and 75 years of age with hepatitis C and signs and symptoms of
cryoglobulinemic vasculitis may be eligible for this study. They must have failed, or been
unable to tolerate, treatment with IFN-a and ribavirin. Candidates will be screened with a
history and physical examination, electrocardiogram (ECG), blood and urine tests, 24-hour
urine collection and chest X-ray, if clinically indicated.
Participants will be randomly assigned to receive Rituximab upon entering the study or 6
months after entering the study. Those whose treatment is delayed 6 months will be followed
once a month at NIH for disease evaluation and blood tests during that time.
Patients will be given Rituximab intravenously (through a vein) once a week for 4 weeks. For
the first dose, patients will be admitted to the hospital for at least 24 hours after the
infusion for monitoring. Subsequent infusions will be given on an inpatient or outpatient
basis, depending on how the infusion is tolerated. The day before each infusion they will
have a history and physical examination, blood work, and other tests, such as X-rays, as
After the four infusions, patients will be followed for drug side effects and response to
treatment. They will have blood tests every week for 4 weeks and will then return to NIH for
1 day every month for 12 months for a physical examination, blood tests, and X-rays, if
medically indicated. Visits may be more frequent, if necessary, and patients may be asked to
stay longer than a day if test findings requ...
The purpose of this study is to assess the safety and efficacy of Rituximab (anti-CD20) in
the treatment of patients with hepatitis C associated cryoglobulinemic vasculitis (HCV-CV)
who have failed or are intolerant to interferon-alpha/ribavirin therapy. Up to 75 patients
may be screened to enroll 34 adult patients with active HCV-CV in this randomized,
non-blinded phase I/II trial. Patients will be randomized to receive either Rituximab 375
mg/M(2) on days 1, 8, 15 and 22 beginning at the time of enrollment or 6 months following
enrollment. Patients in both groups will be maintained on stable doses of any
immunosuppressive therapies that they were receiving at the time of enrollment. Response to
Rituximab will be assessed by clinical and laboratory parameters.
- INCLUSION CRITERIA:
Diagnosis of HCV-CV: must have all of the following
HCV infection documented by serology and/or plasma HCV RNA.
One or more organ system with objective evidence of active vasculitis such as:
Glomerulonephritis (defined by the presence of glomerular hematuria and/or new or
Acute peripheral neuropathy.
Detectable cryoglobulins and/or RF.
Failure of treatment with IFN-alpha and ribavirin to control manifestations of HCV-CV OR
intolerance to IFN-alpha/ribavirin regimen.
Patients must have a personal physician responsible for the care of their HCV.
Ages of 18 and 75 years
Willingness to use effective contraception during and for 12 months following Rituximab
treatment. Effective contraception methods include abstinence, surgical sterilization of
either partner, barrier methods such as diaphragm, condom, cap or sponge, or hormonal
Recent (within 4 weeks) initiation of or increase in immunosuppressive therapy.
Active systemic infection (other than hepatitis C).
Pregnancy or breast feeding.
Prior treatment with Rituximab.
Known allergy to murine proteins.
Significant renal insufficiency (creatinine clearance less than 30 ml/min).
Presence of life-threatening HCV-CV; defined as rapidly progressive glomerulonephritis
(defined as a doubling of the serum creatinine over a 3 month period), CNS vasculitis,
cardiac disease due to active vasculitis, or GI vasculitis (defined by ischemic bowel,
perforation, or infarction).
Significant hepatic insufficiency as manifested by Child-Pugh classification of B or C.
History of variceal bleeding, encephalopathy.
History of liver transplantation.
Co-infection with either HBV or HIV.
Any underlying medical condition that in the judgment of the investigator would put the
patient at increased risk for serious infusion-related adverse events.