E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mantle cell lymphoma |
Manttelisolulymfooma |
|
E.1.1.1 | Medical condition in easily understood language |
Tumour in the lymphatic system |
Imusolmukesyöpä |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10026799 |
E.1.2 | Term | Mantle cell lymphoma NOS |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To increase the complete response rate pretransplant in aggressive mantle cell lymphoma by intensified immunochemotherapy with rituximab, high dose Ara-C and dexamethasone. In the Nordic area only high risk patients (MIPI-B) are included, while in the UK all pteints in need of treatment are included. The result in all patients will be compared to a historic control of corresponding patients in the Nordic MCL2 trial. |
Päätarkoituksena on lisätä täydellisten vasteiden määrää manttelisolulymfoomapotilailla käyttäen intensifioitua immunokemoterapiaa sisältäen rituksimabin, suuriannoksisen sytarabiinin ja deksametasonin. Tutkimukseen otetaan Pohjoismaissa korkean riskin (MIBI-B) potilaita, Britanniassa myös muihin riskiluokkiin kuuluvia. Tuloksia verrataan Pohjoismaisen lymfoomaryhmän aiemmalla (MCL2) hoitotukimuksella saatuihin tuloksiin |
|
E.2.2 | Secondary objectives of the trial |
Time to treatment failure
Progression free survival
Overall survival
Toxicity
Evaluation of response with FDG-PET
Evaluation of response with MRD
Stem cell harvest yield
Evaluation of biomarkers for biology and prediction of response and response duration
To establish a biobank
|
Aika hoidon epäonnistumiseen
Progressiovapaa elinaika
Kokonaiselinaika
Toksisuus
PET-vasteen evaluaatio
Jäänöstautivasteen (MRD) evaluaatio
Kantasolukeruun onnistuminen
Biologisten biomarkkereiden evaluaatio ja ennustemerkitys (biopank)
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Age <66 years.
2.Histologically confirmed (according to the WHO classification) mantle cell lymphoma stage II-IV at time of diagnosis. The diagnosis has to be confirmed by phenotypic expression of CD5, CD20 and cyclin D1 or the t(11;14) translocation.
3.Nordic countries: high-risk patients defined by Mantle Cell Lymphoma International Prognostic Index Biological (MIPI-B), in UK all patients in need of treatment.
4.No previous treatment for lymphoma except one cycle of any chemotherapy regimen.
5.WHO performance status of 0 – 2.
6.Life expectancy of more than 3 months.
7.Written informed consent.
|
1.Ikä <66 years.
2.Histologisesti vahvistettu (WHO luokitus), aiemmin hoitamaton stage II-IV manttelisolulymfooma . Diagnoosin varmistus fenotyypityksellä CD5, CD20- ja sykliini D1-positiivisuus ja/tai translokaatio t(11;14).
3.Korkean riskin tauti: Mantle Cell Lymphoma International Prognostic Index Biological (MIPI-B), Britanniassa lisäksi pienemmän riskin tauti kun hoitoindikaatio on olemassa
4.Yksi aiempi kemoterapiasykli hoito-ohjelman käynnistymistä ennen sallitaan
5.Suorituskyky WHO 0 –2.
6.Odotettavissa oleva elinikä vähintään 3 kuukautta.
7.Potilaan kirjallinen suostumus.
|
|
E.4 | Principal exclusion criteria |
1.Severe cardiac disease: NYHA grade 3-4.
2.Impaired liver-, renal-(GFR<50ml/min) or other organ function not caused by lymphoma, which will interfere with the treatment.
3.Pregnancy/lactation
4.Men or women of reproductive potential not agreeing to use acceptable method of birth control during treatment and for six moths after completion of treatment.
5.Any other prior malignancy than non-melanoma skin cancer or stage 0 (in situ) cervical carcinoma.
6.Known seropositivity for HIV, HCV, HBsAg or other active infection uncontrolled by treatment.
7.Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study.
|
1.Vaikea sydänsairaus (grade 3-4).
2.Huomattava maksan, munuaisten (GFR < 50ml/min) tai muun elimen lymfoomasta riippumaton toimintahäiriö, joka vaikeuttaa tutkimushoidon toteuttamista.
3.Raskaus/imetys.
4.Lisääntymisikäisten kieltäytyminen tehokkaasta raskauden ehkäisystä hoidon aikana ja 6 kuukautta hoidon päättymisestä.
5.Aiempi syöpäsairaus, lukuunottamatta non-melanomaattista ihosyöpää ja in-situ kohdunkaulan syöpää.
6.HIV-, HCV-, tai HBsAg –positiivisuus, tai muu aktiivinen kontrolloimaton infektio.
7.Psyykkinen sairaus tai tila joka voi vaikeuttaa potilaan ymmärrystä tutkimusvaatimuksissa.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Complete remission pretransplant |
Täydellisten vasteiden määrä ennen autologista kantasolusiirtoa |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Over all survival
Time to treatment failure
Time to progression
Evaluation of response with FDG-PET and MRD
Stem cell harvest yield
Evaluation of biomarkers for biology and prediction of response and response duration
|
Kokonaiselinaika
Aika hoidon epäonnistumiseen
Progressiovapaa elinaika
PET-vasteen ja jäänöstautivasteen (MRD) evaluaatio
Kantasolukeruun onnistuminen
Biologisten biomarkkereiden evaluaatio ja ennustemerkitys |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every 3 months for 2 years and then every 6 months to 5 years.
FDG-PET evaluation week 15 and 3 months post transplant
MRD evaluation Week 9 and 15 and 3, 6 months posttransplant and then every 6months to 5 years |
3 kuukauden välein 2 vuoden ajan, tämän jälkeen 6 kuukauden välein 5 vuoteen saakka. PET-tutkimus viikolla 15 ja 3 kuukautta kantasolusiirron jälkeen. Jäännöstautiamittaus viikolla 9 ja 15 sekä 3 ja 6 kuukautta kantasolusiirron jälkeen, tämän jälkeen 6 kuukauden välein 5 vuoteen saakka |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Pohjoismaisen lymfoomaryhmän aiemmat tutkimukset historiallisena kontrollina |
historic control Nordic lymphoma studies |
|
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |