E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced stage, asymptomatic, non-bulky follicular lymphoma (grades 1, 2 and 3a) |
|
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 patients with asymptomatic, advanced stage, non-bulky follicular lymphoma it is common practice to "watch and wait" and by so doing, delay the start of therapy. On average, initiation of treatment is delayed for 2-3 years without any adverse impact on survival. This trial will address the hypothesis that treatment with radiotherapy or chemotherapy can be further delayed by administration at diagnosis of rituximab, a monoclonal antibody. |
|
E.2.2 | Secondary objectives of the trial |
The advantage of watchful waiting for patients with symptomless disease is that the detrimental effects of chemotherapy and radiotherapy can be avoided until the first sign of progression occur. This approach has generally been assumed to result in a better quality of life than immediate treatment. However some patients find it psychologically difficult to be told they have incurable disease and not received immediate treatment. This trial will therefore measure qualilty of life in all arms. Survival and responses to subsequent therapy will also be determined in each arm. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- min. age 18 years, no upper limit - follicular lymphoma grade 1,2 and 3a - stage II, II and IV disease - asymptomatic without "B" symptoms or severe pruritus - blood count : Hb more than 10g/dl, Neuts more than 1,5 x 109/l, PLT more than 100 x 109/l and less than 5 x 109/l circulating tumour cells - renal functions: creatinine less than 2 x UNL for reasons other than lymphoma - normal liver function - Low tumour burden defined as: LDH within normal range largest nodal or extranodal mass less than 7 cm no more than 3 nodal sites with a diameter more than 3 cm not significant serious effusions detectable clinically or on chest X-ray spleen enlargement less than or equal to 16 cm by CT - no other (non-lymphoma) immediately life-threatening disease - must have the disease measurable in at least 2 dimension either clinically or radiologically - entry within 3 months of biopsy with no prior therapy - ECOG performance status 0-1 - no evidence of histological transformation - no second malignancy unless treated with curative intent and patient has been disease-free for more than 2 years - if second malignancy was basal cell carcinoma or squamouus cell carcinoma of the skin or carcinoma of the cervix, the patient need only be currently disease-free - patient must be able to give informed consent - no critical organ failure or organ compression |
|
E.4 | Principal exclusion criteria |
- patients with known to be HIV positive - patients with Hepatitis B infection (required tests - see appendix 3) - pregnant or breastfeeding patients - women of childbearing potential not willing to take adequate contraceptive precautions if randomised to rituximab containg arm |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the time until initiation of therapy (chemotherapy or radiotherapy). This endpoint is defined as the time from randomisation until the first day systemic chemotherapy or radiotherapy is given. If rituximab is given to patients in the watch and wait arm this will be considered as initiation of chemotherapy. |
|
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 | Yes |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | 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 |
|
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.8.5 | The trial involves multiple Member States | Yes |
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 | 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
| |
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 | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |