E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Maintenance therapy in patients carriying a mantle cell lymphoma as response. |
Traitement d'entretien de patients porteur d'un lymphome du manteau en réponse. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061275 |
E.1.2 | Term | Mantle cell lymphoma |
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 |
The primary objective of the study is to demonstrate the superiority in terms of 4-year event-free survival (EFS) of Rituximab maintenance therapy compared to post-autograft surveillance in patients aged 18-65 years inclusive, treated with R-DHAP then autologous transplantation for MCL as first-line therapy. |
L’objectif principal de l’étude est de démontrer la supériorité en terme de survie sans événement (event free survival : EFS) d’un traitement d’entretien par Rituximab versus une surveillance en post-autogreffe chez les patients de moins de 65 ans traités par R-DHAP puis autogreffe pour un LCM en première ligne.Please enter information in other language that is applicable |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the duration of progression-free survival of the entire group of patients.
To evaluate the duration of overall survival of the entire group of patients.
To evaluate the complete, partial and overall response rate after induction with R-DHAP and after ASCT.
|
Evaluer la durée de la survie sans progression pour l’ensemble des patients
Evaluer la durée de la survie globale pour l’ensemble des patients
Evaluer le taux de réponse complète, partielle, globale à l’issue de l’induction par R-DHAP et après l’ACS
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Confirmation of the diagnosis of mantle cell lymphoma according to the WHO classification, including all these variants: typical forms and blastoid variants.
• Initial minimal immunophenotyping is mandatory and will include CD20 and CD5.
• CD20+.
• With the presence of the t (11;14) demonstrated by karyotyping, FISH, molecular biology or immunohistochemistry (by detecting Bcl-1).
•Patient receiving first-line chemotherapy.
•With at least one tumor site accessible for assessment, not just bone marrow involvement. Patients with only blood and bone marrow and/or splenic involvement are excluded.
•Aged between 18 years and 65 years inclusive.
•ECOG 0-1 or 2.
•No other neoplasms apart from resected basal cell carcinoma or in situ carcinoma.
•Patients who have signed an informed consent form.
•Ventricular ejection fraction >=50% measured using an ultrasound or radionuclide method.
•No contraindication to the use of the drugs contained in the regimen.
•With the following limits for laboratory values, unless the abnormal values are related to the lymphoma:
- Neutrophil count >=1 G/L
- Platelet count >= 50 G/L
- Transaminases (AST and ALT) <= 3 x normal (N)
- Bilirubin <= 2 x N
-Calculated creatinine clearance >= 50 mL/min
|
Confirmation du diagnostic de lymphome du manteau selon les critères de l’OMS, dans toutes ces variantes : formes classiques et variantes blastoïdes.
• Un immunophénotypage minimal initial est obligatoire et inclura CD20 et CD5
• CD20+
• Avec la preuve de l’existence d’une t (11 ;14) apportée par un caryotype, une étude en FISH ou en biologie moléculaire.
• En première ligne de chimiothérapie.
• Avec au moins un site tumoral accessible à l’évaluation, non exclusivement médullaire. Les patients avec uniquement une atteinte sanguine et médullaire et/ou splénique sont exclus.
• Jusqu’à 65 ans inclus.
• ECOG 0-1 ou 2
• Pas d’autres néoplasies en dehors d’un carcinome basocellulaire réséqué ou d’un néoplasme in situ.
• Ayant signé un consentement éclairé
• Fraction d’éjection ventriculaire >= 50% mesurée par une méthode échographique ou scintigraphique
•Absence de contre indication à l’utilisation des drogues contenues dans le schéma
•Avec les valeurs biologiques limites suivantes sauf si les valeurs pathologiques sont relatives au lymphome :
-Polynucléaires neutrophiles >= 1 G/L
-Plaquettes >=50 G/L
-Transaminases (SGOT et SGPT) <=3 x normale (N)
- Bilirubine <= 2 x N
-Clairance créatinémie calculée >= 50 mL/min
|
|
E.4 | Principal exclusion criteria |
• Other types of lymphoma besides mantle cell lymphoma, according to the WHO classification.
• Patient in relapse, except relapse after localized disease only previously treated by locoregional irradiation or patient who has undergone splenectomy.
• Contraindication to one of the drugs used in the regimen.
• Uncontrolled diabetes.
• HIV + or active hepatitis C or B.
• Poor performance status: ECOG > 3 (see appendices).
• Patient is unable, for whatever reason, to undergo regular surveillance. |
• Autres types de lymphome que lymphome du manteau selon classification OMS • Patient en rechute, sauf une rechute après un stade localisé n’ayant reçu antérieurement qu’une irradiation loco-régionale ou ayant été splénectomisé. • Contre indication à l’une des drogues utilisées dans le schéma • Diabète non équilibré • VIH + ou hépatite C ou B active • Mauvais état général : ECOG > 3 (cf annexes) • Patient n’ayant pas signé de consentement éclairé. • Patient ne pouvant, pour quelques raisons que se soient, être contraint à une surveillance régulière. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is 4-year event-free survival (EFS) (determined using the Kaplan Meier method) of patients who underwent ASCT and were randomized to one of the two arms of the protocol.
|
Le critère de jugement principal est la survie sans événement (EFS) à 4 ans estimée par la méthode de Kaplan Meier des patients ayant bénéficié d’une ACS et ayant été randomisés dans un des deux bras du protocole. |
|
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 |
surveillance ( sans traitement) |
surveillance ( without treatment) |
|
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 91 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
definition ok |
definition ok |
|
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 | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 6 |