E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Indolent Non-Hodgkin Lymphomas, in particular follicular lymphomas, as well as marginal zone lymphomas, immunocytomas (Waldenström’s macroglobulinaemia) and mantle cell lymphomas |
|
E.1.1.1 | Medical condition in easily understood language |
Slow growing lymph node cancers of different subtypes |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
In follicular lymphomas:
determination and comparison of progression free survival (PFS) with Bendamustine plus Rituximab (B-R) followed by a maintenance therapy with Rituximab over 2 years every 2 months versus Bendamustine plus Rituximab followed by a maintenance therapy with Rituximab over 4 years every 2 months.
In mantle cell lymphomas, marginal zone lymphomas, immunocytomas (Waldenström´s macroglobulinaemias):
determination and comparison of progression free survival with Bendamustine plus Rituximab followed by observation versus Bendamustine plus Rituximab followed by a maintenance therapy with Rituximab over 2 years every 2 months. |
|
E.2.2 | Secondary objectives of the trial |
Efficacy, overall response rates and duaration, event-free-survival, progression-free-survival, disease-free-survival, overall-survival, toxicity, acute and long-term toxicity, incidence of infectious complications. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with histological verified CD20-positive B-cell-lymphoma of the following entities:
follicular lymphoma
immunocytoma / Waldenström’s macroglobulinaemia and small-cell lymphocytic lymphoma without leukaemic phase of the disease
marginal zone lymphoma
mantle cell lymphoma
no pretreatment with cytostatics, interferon or monoclonal antibodies
in need for therapy, except mantle cell lymphoma
stages III or IV or stage II bulky disease
performance status (WHO) 0-2
minimum age 18 years maximum age 80 years
negative pregnancy test, contraception for women of child-bearing age
histology not older than 6 month – mandatory
patients written informed consent |
|
E.4 | Principal exclusion criteria |
Patients not meeting the criteria of E 3
Potential curative radiotherapy as alternative option
Pre-treatment except singular locally confined radiotherapy (radiation field not larger than two adjacent lymph node regions)
concomitant disease which impedes the study equitable therapy like: severe, medicinal uncontrollable hypertension, severe disorder of the heart or lung or liver or kidney, except if caused by the lymphoma
patients with proven HIV-infection
active and replicating hepatitis-infection
severe psychiatric disorder
missing or anticipation of missing compliance
Pregnant or breastfeeding women
Patients with a second malignoma or malignant disease in their history, if surgery is anticipated not to be curable. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Follow up until progression is documented |
|
E.5.2 | Secondary end point(s) |
Remission rates and duration
EFS, PFS, DFS, OS,
Toxicity: acute, long term, infectous complications, immune status |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every two months during maintenance, every 6 months after completion of maintenance |
|
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) | 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 | No |
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 |
Duration of therapy / no therapy |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 150 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 156 |
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
|
Provides in the protocol, section 9.5 |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 1 |