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FDA Approval for Rituxan + Fludarabine/Cyclophosphamide for CLL

doi: 10.1097/

The FDA has approved the use of Rituxan (rituximab) in combination with fludarabine and cyclophosphamide (FC) for people with previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL).

The approval is based on data from two Phase III studies, CLL8 and REACH. Sponsored by Roche and conducted by the German CLL Study Group, the first was a global, multicenter, randomized, open-label, Phase III study that enrolled 817 patients with previously untreated CD20-positive CLL. REACH was a global, multicenter, randomized, open-label, Phase III study sponsored by Genentech, Biogen Idec, and Roche that enrolled 552 patients with previously treated CD20-positive CLL who had not previously received rituximab.

Both studies evaluated rituximab plus FC compared with FC alone, with the primary endpoint of progression-free survival and secondary endpoints of overall and event-free survival, duration of response, response rate, complete response, and toxicity.

Rituxan, discovered by Biogen Idec, first received FDA approval in November 1997 for the treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma (NHL) as a single agent. It was approved in the European Union under the trade name MabThera in June 1998. The drug is also approved for the treatment of NHL for the following:

  • Previously untreated follicular, CD20- positive, B-cell NHL in combination with CVP chemotherapy.
  • Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent, after first-line CVP chemotherapy.
  • Previously untreated diffuse large B-cell, CD20-positive, NHL in combination with CHOP or other anthracycline-based chemotherapy regimens).

Rituxan received FDA approval for rheumatoid arthritis in February 2006 and is currently indicated in combination with methotrexate for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had inadequate response to one or more tumor necrosis factor antagonist therapies.

Genentech and Biogen Idec co-market Rituxan in the United States, and Roche markets MabThera in the rest of the world, except Japan, where Rituxan is co-marketed by Chugai and Zenyaku Kogyo Co., Ltd.

Rituximab has serious side effects, some which can be life-threatening, including infusion reactions, tumor lysis syndrome, severe mucocutaneous reactions, progressive multifocal leukoencephalopathy, hepatitis B infection that may become active again, other infections, heart problems, serious kidney problems, and serious stomach and bowel problems.

The most common side effects in clinical trials of patients with CLL receiving rituximab were side effects from the infusion and low blood cell counts. Most side effects from the infusion happened within 24 hours of the start of the infusion, and included nausea, fever, chills, low blood pressure, vomiting, and difficulty breathing.

Most patients had at least one serious side effect. CLL patients who were older than 70 had more serious side effects compared with those 70 or younger. The most frequently reported serious side effect was low blood cell counts.

© 2010 Lippincott Williams & Wilkins, Inc.
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