You are correct, Awol.
The FDA approved the use of rituximab in the USA for two forms of vasculitis on 4/19/2011.
http://www.cancer.gov/cancertopics/druginfo/fda-rituximab FDA Approval for RituximabBrand name(s): Rituxan®
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.
Approved for Maintenance Therapy for Untreated Follicular CD-20 Positive B-cell Non-Hodgkin LymphomaOn January 28, 2011, the
U.S. Food and Drug Administration (FDA) approved
rituximab (Rituxan®, made by Genentech, Inc.) for
maintenance therapy for patients with previously untreated follicular CD-20 positive
B-cell non-Hodgkin lymphoma who achieve a response to rituximab in combination with
chemotherapy.
The approval was based on the Primary Rituximab and Maintenance (PRIMA) study, an open-label multinational
randomized Phase III study evaluating the benefit of rituximab maintenance therapy. Patients with previously untreated
follicular lymphoma with high tumor burden were randomly assigned to receive either rituximab maintenance therapy or no maintenance therapy after achieving a response to a chemotherapy regimen including rituximab.
After achieving a complete or
partial response to a rituximab plus chemotherapy induction regimen, 1018 patients were randomly assigned (1:1) to receive either rituximab 375 mg/m2, intravenously, every 8 weeks (maximum 12 doses) or observation. Forty percent of patients were over 60 years of age, 70 percent had stage IV disease, 96 percent had Eastern Cooperative Oncology Group (ECOG)
performance status of 0-1, and 42 percent had FLIPI (follicular lymphoma international prognostic index) scores of 3-5. Induction therapy consisted of R-CHOP (rituximab,
hydroxydaunorubicin [doxorubicin], Oncovin [
vincristine], and
prednisone) in 75 percent of patients, R-CVP (rituximab,
cyclophosphamide, vincristine, and prednisone) in 22 percent of patients, and R-FCM (rituximab,
fludarabine, cyclophosphamide, and
mitoxantrone) in 3 percent of patients
Progression-free survival (PFS), evaluated by an independent review committee, was the trial's
primary endpoint. Maintenance rituximab reduced the risk of a PFS event by 46 percent (stratified
hazard ratio: 0.54, 95 percent confidence interval: 0.42-0.70; stratified log-rank test p <0.0001). Results for overall survival remain immature at this time.
Safety data collection was limited to grade ≥2 infections and grade ≥3 adverse reactions. Among 501 patients who received at least one dose of rituximab maintenance therapy, infections were reported in 37 percent. In contrast, infections were reported in 22 percent of patients in the observation group. Grade 3-4 adverse reactions occurred more frequently in rituximab-treated patients, with serious or life-threatening infections occurring in four percent of patients treated with rituximab compared with one percent of patients in the observation group, and moderate to severe
neutropenia occurring in four percent of patients treated with rituximab, compared with less than 1 percent of patients in the observation group.
Back to Top_________________________________________________
Approved for Chronic Lymphocytic Leukemia (CLL)On February 18, 2010, the Food and Drug Administration (FDA) granted approval to rituximab (Rituxan®, made by Genentech), in combination with fludarabine and cyclophosphamide (FC), for the treatment of both previously untreated and previously treated patients with chronic lymphocytic leukemia (CLL). The approval was based on clinically meaningful and statistically significant increases in
progression-free survival (PFS) observed in two randomized multicenter open-label trials in patients randomly assigned to receive either FC or the combination of FC with rituximab (R-FC).
In both studies, patients received intravenous (i.v.) fludarabine 25 mg/m2/day and cyclophosphamide 250 mg/m2/day, daily for 3 days, repeated every 28 days for a total of 6 cycles. Rituximab 375 mg/m2 by i.v. infusion was administered on day 1 of the first cycle (the day before chemotherapy) and 500 mg/m2 i.v. on day 1 of subsequent cycles (on the same day as chemotherapy). The primary efficacy outcome was PFS, defined as the time from randomization to disease progression, relapse, or death. Secondary endpoints included
overall survival (OS) and overall response rates, as determined by the 1996 National Cancer Institute-sponsored Working Group Guidelines.
Study ML17102, also known as CLL8, was conducted by the German CLL Study Group and enrolled patients who were previously untreated. A total of 408 patients were randomly assigned to the R-FC arm and 409 patients to the FC arm. The median age was 61 years (30 percent were 65 years or older), 74 percent were male, 31 percent were Binet stage C, 45 percent had B symptoms, and more than 99 percent had ECOG performance status (PS) 0-1.
The primary efficacy endpoint was PFS, as determined by the investigators. The median PFS were 39.8 months in the R-FC arm and 31.5 months in FC arm [HR 0.56 (95 percent CI: 0.43, 0.71), p <0.01]. Overall response rates were 86 percent (95 percent CI 82, 89) in the R-FC arm and 73 percent (95 percent CI 68, 77) in the FC arm.
Study BO17072, also known as REACH, conducted by Roche and Biogen Idec, enrolled 552 patients with relapsed or refractory CLL following prior systemic therapy. Patients were randomly selected to receive either R-FC (n=276) or FC (n=276). The median age was 62 years (44 percent were 65 years or older), and 67 percent were male. Eighty-two percent had received a prior alkylator-containing regimen and 18 percent had received a fludarabine-containing regimen. “B” symptoms were present in 28 percent, and all patients had ECOG PS 0-1.
The median PFS was 26.7 months for the R-FC arm and 21.7 months for the FC arm, as determined by an independent review committee [HR 0.76 (95 percent CI: 0.60, 0.96), p= 0.022,]. Overall response rates were 54 percent (95 percent CI: 48, 60) in the R-FC arm and 45 percent (95 percent CI: 37, 51) in the FC arm.
Too few events had occurred by the time of regulatory submission to conduct a meaningful analysis of OS in either study. Follow-up of patients for OS is ongoing.
Across both studies, 100 patients who received R-FC and 89 patients who received FC were at least 70 years old. The results of exploratory analyses in this elderly population did not suggest a treatment benefit for the addition of Rituxan to FC in either the previously untreated [HR 1.17 (95 percent CI: 0.51, 2.66)] or previously treated [HR 1.22 (95 percent CI: 0.73, 2.04)] settings.
The safety of rituximab when combined with FC was assessed in 676 patients who received the R-FC regimen. In both studies, 71 percent received 6 cycles and 90 percent received at least 3 cycles of Rituxan-based therapy. Grade 3-4 infusion reactions occurred in 7-9 percent of R-FC treated patients. The following Grade 3-4 adverse events were more frequently observed in the R-FC arm compared to the FC arm: neutropenia, febrile neutropenia, leucopenia, thrombocytopenia, hypotension, hepatitis B, and pancytopenia.
Back to Top_________________________________________________
Low-grade or follicular B-cell, CD20-positive NHLOn September 29, 2006, the the U.S. Food and Drug Administration (FDA) granted approval to rituximab (Rituxan®, made by Genentech, Inc.) for use in the first-line treatment of patients with low grade or follicular B-cell, CD20-positive non-Hodgkin’s lymphoma. One approval was for the use of rituximab combined with CVP chemotherapy (cyclophosphamide, vincristine, and prednisone); the second is for use of rituximab following CVP chemotherapy.
The first indication was based on a 322 patient study. Patients had an advanced-stage, follicular, CD20+ NHL and were previously untreated with chemotherapy. Patients were randomized (1:1) to receive either a maximum of eight three-week cycles of CVP chemotherapy alone or CVP chemotherapy in combination with rituximab (375 mg/m2 on day 1 of each 21-day cycle).
Patients receiving rituximab plus CVP showed a statistically significant improvement in
progression-free survival (PFS) compared to those receiving CVP alone (median PFS 2.4 vs. 1.4 years; hazard ratio 0.44, p<0.0001 two-sided stratified log rank test).
The second indication was based on a 322 patient trial enrolling previously untreated low-grade, B-cell NHL (IWF Grades A, B or C) patients with stable disease or partial or complete responses following six to eight CVP chemotherapy cycles. Patients were randomized (1:1) to receive either no additional therapy or rituximab (375 mg/m2 once weekly for four doses) every six months for up to 16 doses.
A
statistically significant reduction in PFS was observed; the hazard ratio for reduction in the risk of progression, relapse, or death ranged from 0.36 to 0.49 for rituximab versus those who received no additional treatment.
The safety profile observed in these trials was consistent with the previously described safety profile provided in the product label.
Back to Top_________________________________________________
Diffuse large B-cell, CD20-positive NHLOn February 10, 2006, the FDA granted approval to rituximab for use in the
first-line treatment of patients with
diffuse large B-cell, CD20-positive, non-Hodgkin’s lymphoma in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or other
anthracycline-based chemotherapy regimens.
Safety and efficacy were demonstrated in three
randomized, active-controlled,
open-label, multicenter studies with a collective enrollment of 1,854 patients. These trials enrolled primarily patients with diffuse large B-cell lymphoma who had not received prior therapy.
Two of the three studies (E4494 and LNH 98-5/GELA) were restricted to patients 60 years of age or greater, while the third (M39045/MiNT) enrolled patients between ages 18 and 60 years. In E4494 and LNH98-5, the majority of patients had stage III-IV disease, while the majority had stage I-II disease in M39045. Patients received rituximab 375 mg/m2 by differing schedules in combination with CHOP or other anthracycline-based chemotherapy regimens (R-CHEMO).
Each study utilized composite time-to-event
endpoints, incorporating disease progression events as the main outcome measure and included
overall survival among secondary analyses. Determination of the primary endpoint was based upon investigator-assessment.
In each study, hazard ratios for the main outcome measures favored the rituximab-containing arms. In addition, each study showed an overall survival benefit among patients receiving rituximab. With two years of follow-up, more patients were alive by Kaplan-Meier estimates in the rituximab-containing versus control arms for each study as follows: 74 percent vs. 63 percent, 69 percent vs. 58 percent, and 95 percent vs. 86 percent.
In one of the studies, five-year data were available and demonstrated that the survival advantage persisted with estimated five-year survival rates of 58 percent vs. 46 percent for R-CHOP and CHOP, respectively. Results were generally consistent across subgroups, including age, gender and disease prognostic variables.
There was neither additional improvement in progression-free survival nor overall survival for patients in E4494 receiving R-CHOP who were subsequently randomized to additional rituximab after achieving a
complete or
partial response as compared to those who received R-CHOP alone.
In all three studies, the dose intensity for rituximab in the R-CHOP and R-CHEMO induction arms was high and rituximab treatment was not associated with a reduction in the dose intensities of individual chemotherapy components.
Adverse events associated with rituximab were generally consistent with the labeled adverse reactions described for single-agent rituximab. Grade 3/ 4 adverse events occurring with ≥ 2 percent excess in the rituximab arm in at least one study included infection,
thrombocytopenia, and lung toxicity/dyspnea.
The following serious adverse reactions, some with fatal outcomes, have been reported in patients receiving rituximab: severe or fatal infusion reactions, tumor lysis syndrome, severe mucocutaneous reactions, hepatitis B reactivation with fulminant hepatitis, other viral infections, hypersensitivity reactions, cardiac arrhythmias, renal (kidney) toxicity, and bowel obstruction and perforation.
Back to Top_________________________________________________This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "
Understanding the Approval Process for New Cancer Treatments.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.
See also:
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm251946.htmFDA NEWS RELEASE
For Immediate Release: April 19, 2011
Media Inquiries: Morgan Liscinsky, 301-796-0397 ; morgan.liscinsky@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA
FDA approves Rituxan to treat two rare disorders
The U.S. Food and Drug Administration today approved Rituxan (rituximab), in combination with glucocorticoids (steroids), to treat patients with Wegener’s granulomatosis (WG) and microscopic polyangiitis (MPA), two rare disorders that cause blood vessel inflammation (vasculitis).
Vasculitis in patients with WG and MPA can lead to tissue damage. WG mostly affects the respiratory tract (sinuses, nose, trachea, and lungs) and kidneys, while MPA commonly affects the kidneys, lungs, nerves, skin, and joints. Both of these diseases affect people of all ages and ethnicities, and both genders. The causes of these disorders are unknown, and both are considered orphan diseases because they each affect less than 200,000 people in the United States.
“This new indication for Rituxan provides the first approved therapy for these two orphan diseases,” said Curtis Rosebraugh, M.D., M.P.H., director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research.
Rituxan is an antibody that is manufactured through biotechnology methods. The drug works by greatly reducing the number of specific immune cells in the blood, known as B cells.
The safety and effectiveness of Rituxan was demonstrated in a single controlled trial, in which 197 patients with WG or MPA were assigned at random to receive either Rituxan plus glucocorticoids once a week for four weeks or oral cyclophosphamide plus glucocorticoids daily to induce remission. After six months, 64 percent of patients treated with Rituxan had complete remission compared to 53 percent of patients treated with cyclosphosphamide.
Retreatment with Rituxan was not formally evaluated; therefore, the safety and efficacy of retreatment with subsequent courses of Rituxan has not been established. More data are needed to determine the safety of more than one course of Rituxan and long term safety of use of Rituxan in patients with WG and MPA. These questions will be further evaluated in a required post-marketing study.
Rituxan carries a Boxed Warning for infusion reactions, which can occur during infusion or within 24 hours afterwards. Other Boxed Warnings for Rituxan include rashes and sores in the skin and mouth (severe mucocutaneous reactions); and progressive multifocal leukoencephalopathy, a brain infection that generally is fatal. Rituxan is not recommended for use in patients with severe, active infections.
The most common side effects in study participants with WG and MPA included infection, nausea, diarrhea, headache, muscle spasms, and anemia.
Rituxan, which has been marketed since 1997, is also indicated for the treatment of patients with non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis.
Rituxan is manufactured by San Francisco-based Genentech, a member of the Roche Group.
For more information:
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
#
