E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
nodal follicular lymphoma grade 1 or grade 2 in the clinical stage I or II (Ann Arbor classification) |
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E.1.1.1 | Medical condition in easily understood language |
nodal follicular lymphoma |
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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 | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029603 |
E.1.2 | Term | Non-Hodgkin's lymphoma stage II |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
Evaluation of the rate of morphologic CR in week 18 after standard dose (24 Gy) involved site (IS) radiotherapy (RT) plus Rituximab or low-dose (4 Gy) IS RT in combination with Obinutuzumab in early stage nodal follicular lymphoma (centrally reviewed) |
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E.2.2 | Secondary objectives of the trial |
● Morphologic CR, PR, SD, PD in week 7 and month 6 in patients with initially remaining lymphoma judged by CT/MRI ● Metabolic CR in week 18 in patients with initially remaining lymphoma judged by FDG-PET/CT (centrally reviewed) ● Progression-free survival (PFS) of each treatment arm (2 years after individual treatment start) ● PFS of patients in stage I0 after diagnostic surgery (no remaining lymphoma) treated as the experimental arm (2 years after individual treatment start) ● Toxicity (NCI-CTC criteria, version 5) of all patients ● Relapse rate and pattern of recurrence of each treatment arm at all follow-up visits. ● Overall survival (OS) of each treatment arm (2 years) ● Quality of life according EORTC QLQ C30 and FACT-Lym questionnaires at inclusion and in week 18, month 12, and 24 (each treatment arm)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Centrally reviewed CD20-positive follicular lymphoma grade 1/2 or 3a based on WHO classification (2008) • Untreated (radiation-, chemo- or immunotherapy) nodal follicular lymphoma (including involvement of Waldeyer´s ring) • Age: ≥18 years • ECOG: 0-2 • Stage: clinical stage I or II (Ann Arbor classification) based on FDG-PET Staging • Risk profile: Largest diameter of the lymphoma ≤ 7 cm (sectional images) • Written informed consent and willingness to cooperate during the course of the trial • Adequate bone marrow capacity: ANC ≥ 1.5 x 103/ml, thrombocytes ≥ 100000 x 10 3/ml, hemoglobin ≥ 10 g/dL • Capability to understand the intention and the consequences of the clinical trial • Adequate contraception for men and women of child-bearing age during therapy and 18 months thereafter
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E.4 | Principal exclusion criteria |
● Extra nodal manifestation of follicular lymphoma ● Secondary cancer in the patient's medical history (exclusion: basalioma, spinalioma, melanoma in situ, bladder cancer T1a, non-metastasized solid tumor in constant remission, which was diagnosed >3 years ago) ● Serious disease interfering with a regular therapy according to the study protocol, e.g: congenital or acquired immune-deficiency syndromes, active infections including viral hepatitis, uncontrolled concomitant diseases including significant cardiovascular or pulmonary disease ● Severe psychiatric disease ● Pregnancy / lactation ● Known hypersensitivity against Obinutuzumab or Rituximab drugs with similar chemical structure or any other additive of the pharmaceutical formula of the study drug ● Active hepatitis B infection (inactive hepatitis B infections require additional prophylactic anti-viral medication for 1 year (e.g. Lamivudin, Entecavir, Tenofovir) ● Participation in another interventional trial or follow-up period of a competing trial which can influence the results of this current trial
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E.5 End points |
E.5.1 | Primary end point(s) |
● Morphologic complete response (CR) in week 18 in patients with remaining macroscopic PET positive lymphoma after initial diagnostic biopsy judged by CT |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
● Morphologic CR, PR, SD, PD in week 7 and month 6 in patients with initially remaining lymphoma judged by CT/MRI ● Metabolic CR in week 18 in patients with initially remaining lymphoma judged by FDG-PET/CT ● Progression-free survival (PFS) of each treatment arm (2 years after individual treatment start) ● PFS of patients in stage I0 after diagnostic surgery (no remaining lymphoma) treated as the experimental arm (2 years after individual treatment start) ● Toxicity (NCI-CTC criteria, version 5) of all patients ● Relapse rate and pattern of recurrence of each treatment arm at all follow-up visits. ● Overall survival (OS) of each treatment arm (2 years) ● Quality of life according EORTC QLQ C30 and FACT-Lym questionnaires at inclusion and in week 18, month 12, and 24 (each treatment arm)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
week 7, week 18, month 6, month 12 and 24 |
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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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 15 |
E.8.5 | The trial involves multiple Member States | No |
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 | 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
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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 | |
E.8.9.1 | In the Member State concerned days | |