Summary of the risk management plan (RMP) for Oncaspar (pegaspargase)

Transcription

1 EMA/829065/2015 Summary of the risk management plan (RMP) for Oncaspar (pegaspargase) This is a summary of the risk management plan (RMP) for Oncaspar, which details the measures to be taken in order to ensure that Oncaspar is used as safely as possible. For more information on RMP summaries, see here. This RMP summary should be read in conjunction with the EPAR summary and the product information for Oncaspar, which can be found on Oncaspar s EPAR page. Overview of disease epidemiology Oncaspar is used to treat acute lymphoblastic leukaemia (ALL), a cancer of white blood cells called lymphoblasts. ALL is more common in children than in adults. About 1 in 100,000 adult persons per year gets this disease. In children this rate is between 2 and 4 per 100,000 persons per year. The average age of children with ALL is 4.9 years. Slightly more boys than girls are affected. In adults, half the cases are in patients under the age of 50, and ALL is rare over the age of 70. Summary of treatment benefits In a study in 118 children newly diagnosed with ALL, 75% of those treated with Oncaspar (in combination with multi-agent chemotherap) were free of the cancer after 7 years without having relapse or a new cancer. This compares with 66% of those treated with another asparaginase. In another study of 76 children whose cancer returned after earlier treatment, around 40% of Oncaspar-treated patients (some of whom were allergic to other asparaginase treatments) were cleared of the cancer, compared with 47% of patients treated with an asparaginase comparator. Unknowns relating to treatment benefits Data in elderly patients, patients with severe liver and kidney impairment and in pregnant or breastfeeding women are limited. There is also limited information regarding adverse events following intravenous (into a vein) administration, long-lasting adverse events and effects on fertility. Summary of safety concerns Important identified risks Risk What is known Preventability Allergic reactions (hypersensitivity including severe hypersensitivity and Allergic reactions are common side effects with Oncaspar. These reactions are more common after starting treatment and the risk Patients who were previously allergic to Oncaspar should not be started on Oncaspar treatment. Patients should be monitored for Page 1/5

2 Risk What is known Preventability anaphylactic reactions) Inflammation of the pancreas (pancreatitis) Abnormally high levels of any or all lipids and/or lipoproteins in the blood (hyperlipidaemia) Bleeding (haemorrhage) Formation of a blood clot (thromboembolic events) High blood (glucose) sugar (hyperglycaemia) increases with the number of Oncaspar doses. Allergic reactions can be life-threatening. Oncaspar may cause various conditions related to the inflammation of the pancreas. Pancreatitis is a very common side effect with Oncaspar (affecting more than 1 in 10 people). Abnormally high levels of lipids and/or lipoproteins are common side effects with Oncaspar (affecting between 1 in 100 and 1 in 10 people). Various effects on the blood s clotting ability (increased bleeding or the formation of blood clots) have been observed with Oncaspar. Various effects on the blood s clotting ability (increased bleeding or the formation of blood clots) have been observed with Oncaspar. Oncaspar may make blood sugar level rise, causing or worsening diabetes. any allergic reaction during the first hour after administration. In cases of serious allergic reactions to Oncaspar, treatment should be stopped and supportive treatment may need to be started depending on the severity of the symptoms. Patients with history of inflammation of pancreas should not take Oncaspar. Blood tests (serum amylase) should be carried out frequently to identify early signs of inflammation of the pancreas. Patients should be informed of the symptoms of pancreatitis, such as persistent abdominal pain. If pancreatitis is suspected, treatment with Oncaspar should be suspended. Enzyme measurements in the blood (serum amylase) should be carried out frequently to identify early signs of inflammation of the pancreas. Oncaspar should not be used at the same time as other medicines associated with an increased risk of bleeding. Patients with history of bleeding during previous therapy with asparaginase medicines must not be given Oncaspar. Relevant blood parameters should be checked regularly. In patients with risk factors for the formation of blood clots, the use of central venous catheters should be avoided. Oncaspar should be stopped in patients with serious thrombotic events. Patients should tell their doctor immediately if signs of high blood sugar such as increased thirst and Page 2/5

3 Risk What is known Preventability urination occur. Blood and urine sugar levels should be measured regularly during and after treatment. Adverse effects on the liver (hepatotoxicity) Decrease in bone marrow production and associated effects (infection) Damage to the nervous system (neurotoxicity) Adverse effects on the development of the unborn child (embryotoxicity and teratogenicity) Interactions with anticoagulants, corticosteroids, methotrexate and cytarabine, vincristine and live vaccines, and medicines with increased toxicity due to pegaspargase induced impaired liver metabolism Oncaspar was shown to have adverse effects on the liver, resulting in rare cases in liver failure with fatal outcomes. The administration of Oncaspar is associated with decrease in bone marrow production which may be associated with other adverse effects, including opportunistic infections, potentially with serious outcomes. When this medicine is used in combination with other cancer treatments, central nervous system damage can occur. There are no data on unborn children exposed to Oncaspar. However, adverse events have been seen in experiments where unborn animals have been exposed to asparaginase. Pegaspargase may interfere with activity of several medicines or increase the risks associated with them. When given at the same time as live vaccines, pegaspargase increases the risk of infection. Liver laboratory parameters should be monitored to enable timely intervention. Oncaspar must not be used in patients with severe liver impairment. Monitoring the bone marrow (by checking white blood cells levels) and monitoring for signs of infection followed by timely treatment can minimise the impact of this risk. Patients treated with Oncaspar in combination with other cancer treatments should be carefully monitored for signs of damage to the nervous system (e.g. agitation, depression, hallucination, confusion and drowsiness). Oncaspar should not be used during pregnancy and effective contraception (other than oral contraceptives) must be used during treatment and for at least 6 months after discontinuation of treatment. Concomitant administration of medicines should be carefully considered and liver tests performed regularly. Page 3/5

4 Important potential risks Risk Immune reactions to Oncaspar What is known Antibodies that attach to pegaspargase and thus decrease its effects can occur even in patients without the signs of allergic reactions. (immunogenicity) A set of symptoms including headache, confusion, seizures and visual loss There have been reports of patients who developed a set of symptoms including headache, confusion, seizures and visual loss under a combined chemotherapy treatment which included L-asparaginase. (reversible posterior leukencephalopathy syndrome) Missing information Risk What is known Effects on fertility Safety following the administration into veins (intravenous administration) Adverse events with a long latency Safety of patients with severe liver impairment Safety in patients with kidney impairment Investigations of the effects on fertility have not been conducted with Oncaspar. The risk of allergic reactions increases when Oncaspar is given intravenously compared to when it is administered into the muscle. No long-term clinical studies or studies with long-term follow-up periods have been conducted with Oncaspar. Patients with severe liver impairment have not been included in any of the clinical trials. The data on Oncaspar treatment of patients with impaired kidney functions are limited. However, as this medicine is not excreted via the kidneys, no change of drug metabolism or dosage is foreseen in these patients. Use in elderly patients Dosage adjustments for Oncaspar in elderly patients have not been proposed yet, as the data on the use in this population are limited. No increase in the incidence of any specific adverse event in this population has been identified so far. Summary of risk minimisation measures by safety concern All medicines have a summary of product characteristics (SmPC) which provides physicians, pharmacists and other healthcare professionals with details on how to use the medicine, and also describes the risks and recommendations for minimising them. Information for patients is available in Page 4/5

5 lay language in the package leaflet. The measures listed in these documents are known as routine risk minimisation measures. The SmPC and the package leaflet are part of the medicine s product information. The product information for Oncaspar can be found on Oncaspar s EPAR page. Planned post-authorisation development plan List of studies in post-authorisation development plan Study/activity (including study number) Objectives Safety concerns /efficacy issue addressed Status Planned date for submission of (interim and) final results CAALL-F01: a French protocol for the treatment of acute lymphoblastic leukemia (ALL) in children and adolescents Investigating safety, efficacy, and immunogenicity when pegaspargase is used in the firstline treatment along with multi-agent chemotherapy in children and adolescents PEG-ASP in the first-line treatment along with multi-agent chemotherapy in children and adolescents Planned Final study report: 31 December 2025 A novel pediatric- Inspired regimen with reduced myelosuppressive drugs for adults (aged 18-60) with newly diagnosed ph negative acute lymphoblastic leukemia Investigating safety, efficacy and immunogenicity when pegaspargase is used in the firstline treatment along with multi-agent chemotherapy in adults PEG-ASP in the first-line treatment along with multi-agent chemotherapy in adults with ALL Ongoing Final study report: 31 December 2018 Studies which are a condition of the marketing authorisation Both post-authorisation efficacy studies (PAES) are conditions of the marketing authorisation in order to further define the efficacy and safety of Oncaspar. Summary of changes to the risk management plan over time Not applicable. This summary was last updated in Page 5/5