| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Rituximab maintenance in rituximab-responding patients with untreated, chemotherapy resistant or relapsed follicular lymphoma | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 | | E.1.2 | Level | HLT | | E.1.2 | Classification code | 10025634 | | E.1.2 | Term | Lymphomas unclassifiable malignant | |
| 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 investigate if efficacy with maintenance rituximab for a maximal duŕation of 5 years or until relapse/progression, unacceptable toxicity or death whichever occurs first, is superior to 4 times maintenance with rituximab. | |
| E.2.2 | Secondary objectives of the trial | to assess:
1. the safety of the two schedules
2. pharmacoeconomical aspects
3. evaluation of immunologic response | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | 1. Histologically confirmed follicular lymphoma grade 1, 2, 3a or 3b according to WHO classification
2. CD20 expression on immunohistochemistry
3. Any of the following disease status:
- untreated
- relapsed/progressed
- chemotherapy resistant disease
- stable disease (last administration of the last systemic treatment must be at least 12 weeks before patients registration)
4. Patients previously treated with rituximab or radiolabelled anti CD-20 therapy (either alone or in combiation with cytostatics) must have responded to the anti CD-20 containing regimen (CR or PR). At least 12 months must have elapsed from the last anti CD-20 therapy administration.
5. Patients must have at least one two-dimensionally measurable lesion with greatest transverse diameter ≥ 11 mm in CT scan (MRI is allowed only if CT scan cannot be performed).
6. Patients must give written informed consent before registration
7. Patients must have the capability to understant information given by the investigator on the trial.
8. Age must be ≥ 18 years.
9. Performance status must be ≤ 2 on the WHO performance status
10. Adequate cardiac function (EF ≥ 50%) as assessed by echocardioigraphy or MUGA scan.
11. Patient compliance and geographic proximity that allow proper staging and follow-up.
12. Women not breast feeding, are using effective contraception if sexually active, are not pregnant and agree not to become pregnant during participatioin in the trial and during the 12 months thereafter. A negative pregnancy test is required for women with childbearing potential.
13. Patient has recieved 4 doses of rituximab prior to randomization
14. At least 11 weeks have elapsed from start of rituximab induction therapy prior to randomization.
15. All lesions reported in the On-Study Form have been re-evaluated at restaging prior to randomization procedures.
16. Patient must have reached a PR or CR at restaging prior to randomization | |
| E.4 | Principal exclusion criteria | 1. Patients with prior or concomitant malignancies, except non-melanomatous skin cancer or adequately treated in situ cervical cancer.
2. Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningiosis).
3. Serious underlying medical conditions, which could impair the ability of the patient to participate in the trial (e.g. acute or ongoing infection, HIV-infection, uncontrolled diabetes mellitus, active autoimmune disease).
4. Transformation to high-grade lymphoma (secondary to "low-grade" Follicular Lymphoma).
5. Patients regurarly taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to ≤20 mg /day prednisone for indications other than lymphoma or lymphoma-related symptoms.
6. Systemic tumor therapy in the last 30 days.
7. Treatment in a clinical trial within 30 days prior to trial entry.
8. Serious underlying medical conditioins, which could impair the ability of the patient to participate in the trial
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | | - event free survival (EFS) | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 | The trial involves single site in the Member State concerned | Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 2 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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 | 5 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
