natgillin/translations-raw huggingface dataset:
Virkningen blev hovedsageligt bedømt på antallet af patienter, der gik i “ remission ” (leukæmien forsvandt fra knoglemarven, og antallet af blodlegemer blev bragt helt eller delvist tilbage til det normale niveau).
The main measure of effectiveness was the number of patients who went into ‘ remission’ (clearance of leukaemia from the bone marrow and complete or partial recovery of blood cell counts to normal levels).
Hvor langt var vurderingen af ansøgningen nået, da den blev trukket tilbage?
What was the recommendation of the CHMP at that time?
Efter at CHMP havde vurderet virksomhedens besvarelse af spørgsmålene på listen, var der fortsat visse uafklarede spørgsmål.
Based on the review of the data and the company’ s response to the CHMP list of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Evoltra could not have been approved for the treatment of the treatment of AML in elderly patients.
Hvad anbefalede CHMP på daværende tidspunkt?
What were the main concerns of the CHMP?
På baggrund af gennemgangen af dataene og virksomhedens besvarelse af CHMP' s liste med spørgsmål på tidspunktet for tilbagetrækningen af ansøgningen havde CHMP visse betænkeligheder og var af den foreløbige opfattelse, at Evoltra ikke kunne have været godkendt til behandling af AML hos ældre patienter.
The CHMP was concerned that the main study was not sufficient to establish the benefit of Evoltra in the treatment of AML in elderly patients who were unsuitable for intensive chemotherapy, and that the results of a study comparing Evoltra with standard treatment would be necessary to determine the medicine’ s effectiveness.
Der var også betænkeligheder med hensyn til lægemidlets bivirkninger i nyrerne.
There were also some concerns over the medicine’ s side effects affecting the kidneys.
På tilbagetrækningstidspunktet var det derfor CHMP' s opfattelse, at fordelene ved Evoltra ikke var blevet tilstrækkeligt påvist, og at de eventuelle fordele ikke opvejede de påviste risici.
Therefore, at the time of the withdrawal, the CHMP’ s view was that a benefit of Evoltra had not been sufficiently demonstrated and any benefits did not outweigh the identified risks.
Det får ingen konsekvenser at anvende Evoltra til den godkendte indikation, for hvilken benefit/ risk - forholdet forbliver uændret.
There are no consequences on the use of Evoltra in the authorised indication, for which the balance of benefits and risks remains unchanged.
Evoltra er et koncentrat, som blandes til en opløsning til infusion (drop i en vene).
Evoltra is a concentrate that is made up into a solution for infusion (drip into a vein).
Evoltra anvendes til behandling af børn med akut lymfoblastisk leukæmi (ALL), som er en form for kræft i lymfocytterne (en type hvide blodlegemer).
Evoltra is used to treat children with acute lymphoblastic leukaemia (ALL), which is a cancer of the lymphocytes (a type of white blood cell).
Det anvendes til patienter, der ikke har haft effekt af behandling, eller som har fået tilbagefald efter mindst to tidligere behandlinger, og når ingen andre behandlingsformer forventes at være virksomme.
It is used when the disease has not responded to or has come back (relapsed) after at least two other treatments, and when no other treatment is expected to work.
Evoltra er blevet undersøgt hos patienter, som var under 21 år, da de første gang fik ALL.
Evoltra has been studied in patients less than 21 years old when they first became ill with ALL.
Den 5. februar 2002 blev Evoltra udpeget som lægemiddel til sjældne sygdomme, fordi ALL anses for at være sjælden, og der kun findes få patienter, som har sygdommen.
Because the number of patients with ALL is low, the disease is considered ‘ rare’, and Evoltra was designated an ‘ orphan medicine ’ (a medicine used in rare diseases) on 5 February 2002.
Behandling med Evoltra skal overvåges og påbegyndes af læger, som har erfaring i behandling af patienter med akut leukæmi.
Evoltra treatment should be started and supervised by a doctor who has experience in the management of patients with acute leukaemia.
Den anbefalede dosis er 52 mg pr. kvadratmeter legemsoverflade (beregnet ud fra barnets højde og vægt).
The recommended dose is 52 mg per square metre body surface area (calculated using the child ’ s height and weight).
Det gives som en infusion, der varer i to timer, hver dag fem dage i træk.
It is given by infusion lasting two hours every day for five days.
Behandlingen skal gentages hver anden til sjette uge.
The treatment should be repeated every two to six weeks.
De fleste patienter, som responderer på behandling, opnår respons efter en til to behandlingscykler.
Most patients who respond to treatment do so after one or two treatment cycles.
Det aktive stof i Evoltra, clofarabin, er et cytotoksisk lægemiddel, som tilintetgør celler, der deler sig, for eksempel kræftceller.
The active substance in Evoltra, clofarabine, is a cytotoxic (a medicine that kills cells that are dividing, such as cancer cells).
Det tilhører en gruppe af lægemidler mod kræft, som kaldes ” antimetabolitter ”.
It belongs to the group of anti-cancer medicines called ‘ antimetabolites’.
Clofarabin er en analog til adenin, som er en del af cellernes grundlæggende genetiske materiale (DNA og RNA).
Clofarabine is an ‘ analogue ’ of adenine, which is part of the fundamental genetic material of cells (DNA and RNA).
Dette betyder, at clofarabin overtager adenins plads i kroppen og interfererer med de enzymer, der er med til at lave det genetiske materiale, kaldet DNA- polymerase og RNA- reduktase.
This means that clofarabine takes the place of adenine in the body, and interferes with the enzymes involved in making genetic material, called ‘ DNA polymerase’ and ‘ RNA reductase’.
Dette forhindrer cellerne i at producere ny DNA og RNA og hæmmer væksten af tumorceller.
This stops the cells making new DNA and RNA, and slows down the growth of tumour cells.
Virkningerne af Evoltra blev først afprøvet i forsøgsmodeller, inden de blev undersøgt hos mennesker.
Reproduction is authorised provided the source is acknowledged. patients had previously received at least two other types of treatment but were not eligible for any other treatment.
Gennemsnitsalderen for de behandlede patienter var 12 år.
The average age of the treated patients was 12 years.
Behandlingens virkning blev hovedsageligt bedømt på antallet af patienter, der gik i ” remission ” (leukæmien forsvandt fra knoglemarven, og antallet af blodlegemer blev helt eller delvist normalt).
The main measure of effectiveness was the number of patients who went into ‘ remission’ (clearance of leukaemia from the bone marrow and complete or partial recovery of blood cell counts to normal levels).
I undersøgelsen blev Evoltra ikke sammenlignet med nogen anden behandling.
The study did not compare Evoltra with any other treatments.
I hovedundersøgelsen gik 20% af patienterne i remission (12 ud af 61).
In the main study, 20% of the patients went into remission (12 out of 61).
Generelt overlevede patienterne i undersøgelsen gennemsnitligt 66 uger.
Overall, the patients in the study survived for an average of 66 weeks.
Efter behandlingen med Evoltra kunne 10 patienter gennemgå en stamcelletransplantation.
After treatment with Evoltra, 10 patients were able to go on to have a stem cell transplant.
Dette er en kompleks proces, hvor patientens knoglemarv, herunder leukæmicellerne, ødelægges og erstattes af stamceller, som på ny ’ koloniserer ’ knoglemarven.
This is a complex procedure where the bone marrow of the patient, including the leukaemia cells, is destroyed and replaced by stem cells that ‘ recolonise’ the bone marrow.
Stamceller er meget unge celler, som normalt dannes i knoglemarven, og som kan udvikle sig til alle typer blodlegemer.
Stem cells are very young cells that are normally made in the bone marrow and can develop into all of the different types of blood cell.
I undersøgelserne var de hyppigste bivirkninger ved Evoltra (som optræder hos flere end 1 ud af 10 patienter) febril neutropeni (lavt antal hvide blodlegemer med feber), angst, hovedpine, rødmen af ansigtet, opkastning, diarré, kvalme, dermatitis (betændelse i huden), pruritus (kløe), pyreksi (feber), betændelse i slimhinderne (såsom betændelse i mundslimhinden) og træthed.
In studies, the most common side effects with Evoltra (seen in more than 1 patient in 10) were febrile neutropenia (low white blood cell counts with fever), anxiety, headache, flushing (reddening of the face), vomiting, diarrhoea, nausea (feeling sick), dermatitis (inflammation of the skin), pruritus (itching), pyrexia (fever), mucosal inflammation (inflammation of the moist body surfaces, such as the lining of the mouth) and fatigue (tiredness).
Den fuldstændige liste over samtlige bivirkninger ved Evoltra fremgår af indlægssedlen.
For the full list of all side effects reported with Evoltra, see the Package Leaflet.
Evoltra bør ikke anvendes til personer, som kan være overfølsomme (allergiske) over for clofarabin eller et af de øvrige indholdsstoffer.
Evoltra should not be used in people who may be hypersensitive (allergic) to clofarabine or any of the other ingredients.
Evoltra må ikke anvendes af patienter med alvorlige nyre - eller leversygdomme.
Evoltra must not be given to patients with severe kidney or liver disease.
Da Evoltra er et cytotoksisk lægemiddel, må det ikke anvendes under graviditet, medmindre det er absolut nødvendigt, og amning bør indstilles både før, under og efter behandling.
Because Evoltra is a cytotoxic medicine, it should not be used during pregnancy unless absolutely necessary and breast-feeding should be stopped before, during and after treatment.
Patienter med ALL, som ikke har responderet på, eller som har haft tilbagefald efter at have modtaget mindst to behandlinger, har en meget lille chance for at overleve.
Patients with ALL who have not responded to or who have relapsed after receiving at least two treatments have a very poor chance of survival.
Udvalget for Humanmedicinske Lægemidler (CHMP) konkluderede, at behandling med Evoltra kan give mulighed for at opnå remission og gøre det lettere at transplantere stamceller.
The Committee for Medicinal Products for Human Use (CHMP) concluded that Evoltra treatment may provide a way of obtaining remission, and of facilitating a stem cell transplant.
Udvalget besluttede, at fordelene ved Evoltra er større end risiciene til behandling af pædiatriske patienter med ALL, hvor sygdommen er kommet tilbage, eller som ikke har været modtagelige for mindst to tidligere behandlinger, og når der ikke findes nogen anden behandlingsmulighed, som forventes at kunne give et varigt respons.
The Committee decided that Evoltra’ s benefits are greater than its risks for the treatment of ALL in paediatric patients who have relapsed or are refractory after receiving at least two prior regimens and where there is no other treatment option anticipated to result in a durable response.
Udvalget anbefalede udstedelse af markedsføringstilladelse for Evoltra.
The Committee recommended that Evoltra be given marketing authorisation.
Evoltra er blevet godkendt under ” særlige omstændigheder ”.
Evoltra has been authorised under ‘ Exceptional Circumstances’.
Dette betyder, at det ikke har været muligt at indhente fyldestgørende oplysninger om lægemidlet, da sygdommen er sjælden.
This means that, because the disease is rare, it has not been possible to obtain complete information about Evoltra.
Virksomheden, der fremstiller Evoltra, skal foretage en undersøgelse af brugen af Evoltra til patienter med nyresygdomme og oprette et register til overvågning af bivirkninger ved lægemidlet.
The company that makes Evoltra will carry out a study to look at the use of Evoltra in patients with kidney disease, and set up a registry to monitor the medicine ’ s side effects.
Hvilke foranstaltninger træffes der for at sikre risikofri anvendelse af Evoltra?
Which measures are being taken to ensure the safe use of Evoltra?
Virksomheden, der fremstiller Evoltra, skal sikre, at læger ved, hvordan Evoltra bedst anvendes, og opfordre dem til at anvende registret til overvågning af bivirkninger ved lægemidlet.
The company that makes Evoltra will make sure that doctors know about the best way to use Evoltra, and encourage them to use the registry for monitoring side effects.
Andre oplysninger om Evoltra:
Other information about Evoltra:
Europa- Kommissionen udstedte en markedsføringstilladelse med gyldighed i hele Den Europæiske Union for Evoltra den 29. maj 2006.
The European Commission granted a marketing authorisation valid throughout the European Union for Evoltra on 29 May 2006.
Indehaveren af markedsføringstilladelsen er Genzyme Europe B. V.
The marketing authorisation holder is Genzyme Europe B. V.
Sammendraget af udtalelsen fra Udvalget for Lægemidler til Sjældne Sygdomme om Evoltra kan ses her.
The summary of opinion of the Committee for Orphan Medicinal Products for Evoltra is available here.
2/ 3 Den fuldstændige EPAR for Evoltra findes her.
The full EPAR for Evoltra is available here.
EU- nummer EU/ 1/ 06/ 334/ 001
EU/ 1/ 06/ 334/ 001
Særnavn Evoltra
Evoltra
Styrke 1 mg/ ml
1 mg/ ml
Paknings- størrelse 3 hætteglas
3 vials
Evoltra 1 mg/ ml koncentrat til infusionsvæske, opløsning
Evoltra 1 mg/ ml concentrate for solution for infusion
Et 20 ml hætteglas indeholder 180 mg natriumchlorid.
Each 20 ml vial contains 180 mg of sodium chloride.
En klar, næsten farveløs opløsning med pH 4, 5 – 7, 5 og osmolaritet 270 – 310 mOsm/ l.
Clear, practically colourless solution with a pH of 4.5 to 7.5 and an osmolarity of 270 to 310 mOsm/ l.
Behandling af pædiatriske patienter med recidiverende eller refraktær akut lymfoid leukæmi (ALL), efter at de har fået mindst to tidligere behandlingsregimer, og hos hvem ingen andre behandlings - former forventes at kunne opnå et varigt respons.
Treatment of acute lymphoblastic leukaemia (ALL) in paediatric patients who have relapsed or are refractory after receiving at least two prior regimens and where there is no other treatment option anticipated to result in a durable response.
5. 1).
Safety and efficacy have been assessed in studies of patients ≤ 21 years old at initial diagnosis (see section 5.1).
Voksne (inklusive ældre patienter):
Adults (including the elderly):
5. 2).
There are currently insufficient data to establish the safety and efficacy of clofarabine in adult patients (see section 5.2).
Den anbefalede dosis er 52 mg/ m2 legemsoverflade og administreres som intravenøs infusion over 2 timer dagligt 5 dage i træk.
The recommended dose is 52 mg/ m2 of body surface area administered by intravenous infusion over 2 hours daily for 5 consecutive days.
Behandlingscyklus gentages hver 2. – 6. uge (beregnet fra første dag i den foregående cyklus), når normal hæmatopoiese er genoprettet (ANC ≥ 0, 75 × 109/ l), og organfunktionen atter er som ved baseline.
ANC ≥ 0.75 × 109/ l) and return to baseline organ function.
Hos patienter med signifikant toksicitet (se nedenfor) kan 25% dosisreduktion være påkrævet.
A 25% dose reduction may be warranted in patients experiencing significant toxicities (see below).
4. 4).
There is currently limited experience of patients receiving more than 3 treatment cycles (see section 4.4).
5. 1).
The majority of patients who respond to clofarabine achieve a response after 1 or 2 treatment cycles (see section 5.1).
4. 4).
Therefore, the potential benefit and risks associated with continued therapy in patients who do not show haematological and/ or clinical improvement after 2 treatment cycles should be assessed by the treating physician (see section 4.4).
Børn (vægt < 20 kg):
Children (weighing < 20 kg):
5. 2).
An infusion time of > 2 hours should be considered to help reduce symptoms of anxiety and irritability, and to avoid unduly high maximum concentrations of clofarabine (see section 5.2).
2 Børn (under 1 år):
2 Children (< 1 year old):
Det har derfor endnu ikke været muligt at fastsætte en sikker og effektiv dosisrekommandation for patienter under 1 år.
Therefore, a safe and effective dosage recommendation for patients (< 1 year old) has yet to be established.
Patienter med nyreinsufficiens:
Patients with renal insufficiency:
Der er ingen erfaring med patienter med nyreinsufficiens (serum - kreatinin ≥ 2 x ULN for aldersgruppen), og clofarabin udskilles hovedsageligt via nyrerne.
There is no experience in patients with renal insufficiency (serum creatinine ≥ 2 x ULN for age) and clofarabine is predominately excreted via the kidneys.
4. 4).
Therefore, clofarabine is contraindicated in patients with severe renal insufficiency (see section 4.3) and should be used with caution in patients with mild to moderate renal insufficiency (see section 4.4).
Der foreligger endnu utilstrækkelige data om clofarabins farmakokinetik hos patienter med nedsat kreatininclearance til at kunne anbefale dosisreduktion hos denne patientgruppe.
To date, there are insufficient data on the pharmacokinetics of clofarabine in patients with decreased creatinine clearance to advise a dose reduction in such patients.
4. 4 og 5. 2).
However, these limited data indicate that clofarabine may accumulate in patients with decreased creatinine clearance (see sections 4.4 and 5.2).
Der er ikke erfaring med patienter med nedsat leverfunktion (serum- bilirubin > 1, 5 x ULN samt ASAT og ALAT > 5 x ULN), og leveren udgør et potentielt målorgan for toksicitet.
There is no experience in patients with hepatic impairment (serum bilirubin > 1.5 x ULN plus AST and ALT > 5 x ULN) and the liver is a potential target organ for toxicity.
4. 4).
Therefore, clofarabine is contraindicated in patients with severe hepatic impairment (see section 4.3) and should be used with caution in patients with mild to moderate hepatic impairment (see section 4.4).
Dosisreduktion hos patienter med hæmatologisk toksicitet:
Dose reduction for patients experiencing haematological toxicities:
Hvis ANC ikke er normaliseret 6 uger efter starten på en behandlingscyklus, bør der udføres knoglemarvsaspiration / - biopsi for at påvise eventuel refraktær sygdom.
If the ANC does not recover by 6 weeks from the start of a treatment cycle, a bone marrow aspirate / biopsy should be performed to determine possible refractory disease.
Hvis der ikke er tegn på persisterende leukæmi, anbefales det at reducere dosis til næste cyklus med 25% i forhold til den forudgående dosis, efter at ANC atter er ≥0, 75 x 109/ l..
If persistent leukaemia is not evident, it is recommended that the dose for the next cycle be reduced by 25% of the previous dose following recovery of ANC to ≥ 0.75 × 109/ l.
Til patienter, hos hvem ANC holder sig < 0, 5 × 109/ l i over 4 uger efter start på den forudgående cyklus, anbefales det at reducere dosis til næste cyklus med 25%.
Should patients experience an ANC < 0.5 × 109/ l for more than 4 weeks from the start of the last cycle, it is recommended that the dose for the next cycle be reduced by 25%.
Dosisreduktion hos patienter med ikke- hæmatologisk toksicitet:
Dose reduction for patients experiencing non-haematological toxicities:
Infektiøse hændelser:
Infectious events:
Hvis en patient udvikler en klinisk signifikant infektion, kan clofarabin seponeres, indtil infektionen er velkontrolleret.
If a patient develops a clinically significant infection, clofarabine treatment may be withheld until the infection is clinically controlled.
I tilfælde af en til klinisk signifikant infektion bør clofarabin seponeres, indtil infektionen er velkontrolleret, og den kan genoptages, hvis dosis reduceres med 25%.
In the event of a second clinically significant infection, clofarabine treatment should be withheld until the infection is clinically controlled and may be reinitiated at a 25% dose reduction.
Ikke- infektiøse hændelser:
Non-infectious events:
Hvis en patient oplever en eller flere alvorlige toksicitetsreaktioner (grad 3 toksicitet ifølge det amerikanske National Cancer Institutes Common Toxicity Criteria (NCI- CTC) eksklusive kvalme og opkastning), skal behandlingen udsættes, indtil laboratorieundersøgelser er vendt tilbage til baselineværdier, eller toksicitetsreaktionerne ikke længere er alvorlige, og de potentielle fordele ved fortsat behandling med clofarabin overstiger risikoen ved at fortsætte.
If a patient experiences one or more severe toxicities (US National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Grade 3 toxicities excluding nausea and vomiting), treatment should be delayed until the toxicities resolve to baseline parameters or to the point where they are no longer severe and the potential benefit of continued treatment with clofarabine outweighs the risk of such continuation.
I sådanne tilfælde anbefales det at reducere doseringen af clofarabin med 25%.
It is then recommended that clofarabine be administered at a 25% dose reduction.
I sådanne tilfælde anbefales det at reducere doseringen af clofarabin med yderligere 25%.
It is then recommended that clofarabine be administered at a further 25% dose reduction.
4. 4).
Any patient who experiences a severe toxicity on a third occasion, a severe toxicity that does not recover within 14 days (see above for exclusions), or a life-threatening or disabling toxicity (US NCI CTC Grade 4 toxicity) should be withdrawn from treatment with clofarabine (see section 4.4).
6. 6).
Evoltra 1 mg/ ml concentrate for solution for infusion must be diluted prior to administration (see section 6.6).
6. 2).
Evoltra must not be mixed with or concomitantly administered using the same intravenous line as other medicinal products (see section 6.2).
3 4. 3 Kontraindikationer
3 4.3 Contraindications
6. 1).
Hypersensitivity to clofarabine or to any of the excipients (see section 6.1).
4. 6).
Breastfeeding should be discontinued prior to, during and following treatment with Evoltra (see section 4.6).
4. 8).
Evoltra is a potent antineoplastic agent with potentially significant haematological and non-haematological adverse reactions (see section 4.8).
Det er derfor vigtigt at overvåge følgende parametre nøje hos patienter i behandling med clofarabin: • Komplet blodstatus og trombocyttal skal indhentes regelmæssigt, dog hyppigere hos patienter, som får cytopeni. • Nyre - og leverfunktion skal kontrolleres før og efter behandlingen samt i løbet af aktiv behandling.
The following parameters should, therefore, be closely monitored in patients undergoing treatment with clofarabine: • Complete blood and platelet counts should be obtained at regular intervals, more frequently in patients who develop cytopenias. • Renal and hepatic function prior to, during active treatment and following therapy.
Clofarabin bør omgående seponeres i tilfælde af voldsomme stigninger i kreatinin eller bilirubin. • Respirationsstatus, blodtryk, væskebalance og vægt bør kontrolleres løbende under og umiddelbart efter de fem dages aktiv behandling med clofarabin.
Clofarabine should be discontinued immediately if substantial increases in creatinine or bilirubin are observed. • Respiratory status, blood pressure, fluid balance and weight throughout and immediately after the 5 day clofarabine administration period.
4. 8).
Patients undergoing treatment with clofarabine should be evaluated and monitored for signs and symptoms of tumour lysis syndrome and cytokine release (e. g. tachypnoea, tachycardia, hypotension, pulmonary oedema) that could develop into Systemic Inflammatory Response Syndrome (SIRS) / capillary leak syndrome or organ dysfunction (see section 4.8).
Clofarabin bør omgående seponeres, hvis patienten udviser nogle af de tidlige symptomer på SIRS / systemisk vaskulær lækage- syndrom eller omfattende organdysfunktion, og passende understøttende behandling iværksættes.
Clofarabine should be discontinued immediately if patients show early signs or symptoms of SIRS / capillary leak syndrome or substantial organ dysfunction and appropriate supportive measures instituted.