E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Untreated patients with follicular lymphoma in need of therapy. |
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E.1.1.1 | Medical condition in easily understood language |
Untreated patients with follicular lymphoma in need of therapy. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025310 |
E.1.2 | Term | Lymphoma |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the activity of the combination of rituximab and lenalidomide given to untreated follicular lymphoma patients versus rituximab treatment. |
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E.2.2 | Secondary objectives of the trial |
Safety of the two therapy arms. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Translational research: Research on biological samples of follicular lymphoma patients searching for prognostic and predictive biomarkers for this disease: -Translocation -FcgR polymorphism & response -Immunophenotyping -Microenvironment -Soluble micr RNA -Immunomodulation & complement inhibition -Endocannabinoid -Signaling pathways -Blood and tumor immune cells by flow cytometry All material required for these projects will be obtained from the biobanks / sample banking. |
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E.3 | Principal inclusion criteria |
-Histologically confirmed FL CD20+; grade 1, 2, 3a; stage III+IV; stage II not suitable for radiotherapy -Patients in need of systemic therapy: (at least one of these indications must be fulfilled) •symptomatic enlarged lymph nodes, spleen or other lymphoma manifestations •bulky disease ≥ 6 cm in long diameter •clinically significant progression over at least 6 months of any tumor lesion •anemia (Hb < 100 g/L) or thrombocytopenia (Platelets < 100 x 109/L) due to lymphoma •clinically significant progressive decrease in Hb or platelet count due to lymphoma •B-symptoms ,weight loss > 10 % in 6 months, drenching night sweats or fever > 38°C not due to infection -Patients must have at least one two-dimensionally measurable lesion with longest transverse diameter > 10 mm -Paraffin embedded tumor tissue is available for sending for pathology review -Age > 18 years -WHO performance status 0-2 -For patients with history of cardiac disease or older than 70 years: adequate cardiac function must be confirmed by EF ≥ 50% -Adequate hematological values unless due to marrow infiltration by FL: (Neutrophils ≥ 1.5 x 109/l, Platelets ≥ 100 x 109/l) -Adequate hepatic function: Bilirubin ≤ 1.5 x ULN (unless due to Gilbert’s syndrome), ALT/AP ≤ 2.5 x ULN -Adequate renal function (calculated creatinine clearance ≥ 30 ml/min, according to the formula of Cockroft-Gault) -Patient must give written informed consent before randomization -Patient compliance and geographic proximity allow proper staging and follow-up -Women with Childbearing potential •are not pregnant and agree not to become pregnant during participation in the trial and during the 12 months thereafter •are using effective contraception since 30 days at least •have a negative pregnancy test within 4 days before randomization -Men agree not to father a child, not to donate semen and to use condoms during trial treatment and 12 months thereafter -Patients (male and female) agree to follow the special pregnancy prevention requirements for Revlimid® (lenalidomide) |
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E.4 | Principal exclusion criteria |
-Previous systemic therapy for follicular lymphoma -Radiotherapy within the last 3 months -Known CNS involvement -Any serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes) -Previous malignancy within 5 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer -Psychiatric disorder precluding understanding information of trial related topics, giving informed consent, or interfering with compliance for oral drug intake -Known hypersensitivity to trial drug(s) or hypersensitivity to any other component of the trial drugs -Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information -Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to trial entry -Known HIV+ infection or HCV infection -Patients with any serological evidence of current or past hepatitis B, unless the serological findings are clearly due to vaccination -Patients regularly taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to Prednisone ≤ 15 mg/day for indications other than lymphoma or lymphoma-related symptoms -Pregnant or lactating females -Patients in need of urgent chemotherapy, e.g. because of existing or imminent compression |
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E.5 End points |
E.5.1 | Primary end point(s) |
Complete response assessed at week 23 (+/- 1 week) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
week 23 (1/- 1 week) after treatment start |
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E.5.2 | Secondary end point(s) |
Best Overall Response (OR) within 24 weeks Best OR within 12 weeks Best OR Progression-free Survival Duration of Complete Response Time to first off-trial anti-lymphoma therapy Overall Survival AEs including lab abnormality assessments and vital signs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During follow-up phase of 10 years |
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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 | 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) | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 | No |
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 |
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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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Last patient last visit refers in this trial to when the last patient had his second restaging and thus is evaluable for the primary endpoint, which is expected to be in Q4 2012. All patients will be followed up for at least 10 years after randomization. Afterwards, in the following 10 years, information on survival, disease status and further treatment may be collected upon request of SAKK without scheduled trial visits. Overall collection of patient data lasts 20 years.
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |