Dear Health Care Professional Letter PrADCETRISTM
Health Canada posts safety alerts, public heath advisories, press releases and other notices from industry as a service to health professionals, consumers, and other interested parties. Although Health Canada authorizes therapeutic products, Health Canada does not endorse either the product or the company. Any questions regarding product information should be discussed with your health professionals.
This is duplicated text of a letter from Seattle Genetics Inc.
Contact Seattle Genetics Inc. for a copy of any references, attachments or enclosures.
Authorization with conditions of
PrADCETRIS (brentuximab vedotin)
for the treatment of patients with:
- Hodgkin Lymphoma (HL) after failure of autologous stem cell transplant (ASCT) or after failure of at least two multi-agent chemotherapy regimens in patients who are not ASCT candidates
- Systemic anaplastic large cell lymphoma (sALCL) after failure of at least one multi-agent chemotherapy regimen
February 1, 2013
Dear Health Care Professional(s),
Health Canada has issued a Notice of Compliance with Conditions under the Notice of Compliance with Conditions (NOC/c) Policy for ADCETRIS (brentuximab vedotin), 50 mg/vial of lyophilized powder for reconstitution for:
- The treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two multi-agent chemotherapy regimens in patients who are not ASCT candidates;
- The treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one multi-agent chemotherapy regimen.
Marketing authorization with conditions under the NOC/c Policy reflects the promising nature of the clinical evidence for ADCETRIS and the need for further follow-up to confirm the clinical benefit.
This NOC/c was based on results from two single-arm, pivotal, phase II trials of ADCETRIS studied in 102 patients with HL and 58 patients with sALCL. Patients were treated with 1.8 mg/kg of ADCETRIS intravenously over 30 minutes every 3 weeks for up to 16 cycles. An independent review facility performed efficacy evaluations, including overall response rate (ORR = complete remission [CR] + partial remission [PR]) and duration of response, which were assessed using clinical and radiographic measures including computed tomography (CT) and positron-emission tomography (PET) as defined in the 2007 Revised Response Criteria for Malignant Lymphoma.
In the phase II HL trial in 102 patients, an ORR of 75% (95% CI: 65, 83) with a median duration of 6.7 months (95% CI: 3.6, 14.8; range: 1.2+ to 26.1+) was observed. A CR of 32% (95% CI: 23, 42) with a median duration not yet reached (95% CI: 12.08, NE; range: 1.4 to 26.1+) was observed.
In the phase II sALCL trial in 58 patients, an ORR of 86% (95% CI: 75, 94) with a median duration of 13.2 months (95% CI: 5.7, NE; range: 0.1 to 21.7+) was observed. A CR of 59% (95% CI: 45, 71) with a median duration not yet reached (95% CI: 13.0, NE; range: 0.7 to 21.7+) was observed.
- Patients who are hypersensitive to ADCETRIS or to any of the ingredients in the formulation or component of the container.
- Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.
- Patients who have or have had progressive multifocal leukoencephalopathy (PML).
Serious Warnings and Precautions
JC virus infection resulting in progressive multifocal leukoencephalophathy (PML) and death can occur in ADCETRIS-treated patients. Contributing factors may include prior therapies and underlying disease that may cause immunosuppression. Healthcare professionals should monitor patients on ADCETRIS for any new signs or symptoms that may be suggestive of PML. Further treatment with ADCETRIS should be withheld immediately at the first sign or symptom suggestive of PML.
Dosage and Administration
The recommended dose is 1.8 mg/kg administered only as an intravenous infusion over 30 minutes every 3 weeks. The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg. Do no administer as an intravenous push or bolus.
Patients who achieve stable disease or better should receive a minimum of 8 cycles and up to a maximum of 16 cycles (approximately 1 year). Continue treatment until disease progression or unacceptable toxicity.
Dosing modification may be needed in the following situations:
- Peripheral Neuropathy: Monitor patients for new or worsening Grade 2 or 3 neuropathy. Dosing should be held until neuropathy improves to Grade 1 or baseline and then restarted at 1.2 mg/kg. For Grade 4 peripheral neuropathy, ADCETRIS should be discontinued.
- Neutropenia: Monitor complete blood counts prior to each dose of ADCETRIS. The dose of ADCETRIS should be held for Grade 3 or 4 neutropenia until resolution to baseline or Grade 2 or lower. Growth factor support should be considered for subsequent cycles in patients who experience Grade 3 or 4 neutropenia. In patients with recurrent Grade 4 neutropenia despite the use of growth factors, discontinuation or dose reduction of ADCETRIS to 1.2 mg/kg may be considered.
- Thrombocytopenia: If Grade 3 or 4 thrombocytopenia develops, monitor closely and consider platelet transfusions or dose delays.
Please see the ADCETRIS (brentuximab vedotin) Product Monograph for the complete necessary information for the safe and effective use of this product.
Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any case of serious or unexpected adverse reactions in patients receiving ADCETRIS should be reported to Seattle Genetics, Inc. or Health Canada.
For any medical inquiries regarding ADCETRIS, please contact the Seattle Genetics, Inc. Medical Information Department at 1-855-473-2436.
Original Signed by:
Thomas C. Reynolds, MD, PhD.
Chief Medical Officer
Seattle Genetics Inc.
Seattle Genetics, Inc.
1215B North Service Road W
Oakville, ON L6M 2W2
You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:
The Reporting Forms, postage paid labels, and Guidelines can be found on the MedEffectTM Canada website in the Adverse Reaction Reporting section. The Reporting Form is also in the Canadian Compendium of Pharmaceuticals and Specialties.
For other health product inquiries related to this communication, please contact Health Canada at:
Biologics and Genetic Therapies Directorate
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