E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Follicular lymphoma
LLT Follicle centre lymphoma, follicular grade I, II, III PT Follicle centre lymphoma, follicular grade I, II, III
MedDRA Version 9
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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 |
The primary objective of this project is to test the safety and efficacy of two fractions of 90Y ibritumomab tiuxetan in patients with previously untreated follicular lymphoma in a Phase II study.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate the progression-free-survival (PFS) and the overall survival time:
• Progression-free-survival (PFS). PFS is defined as the difference between the date of randomization and the date on which the patients progresses or dies from any cause. • Overall survival time. This endpoint is defined as the time interval between the date of randomization and the date of death (from any cause) of the patient.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• Patients must be aged 18 years or older. • Patients must have a histologically confirmed CD20 +ve follicular lymphoma. • Patients with at least one of the following symptoms requiring initiation of treatment: (as outlined by the modified BNLI/GELF criteria below) Nodal mass > 5cm in its greater diameter B symptoms Elevated serum LDH or 2-microglobulin involvement of at least 3 nodal sites (each with a diameter greater than 3 cm) symptomatic splenic enlargement compressive syndrome • Patients must have an ECOG performance status less than or equal to 2 (see Appendix 2) and an anticipated survival of at least 6 months. • Patients must have an absolute granulocyte count of above 1,500/mm3, and a platelet count of above 100,000/mm3 post 4 weeks of unlabelled Rituximab. • Patients must have adequate renal function (defined as serum creatinine <1.5 times upper limit of normal), hepatic function (defined as total bilirubin <1.5 times upper limit of normal), and hepatic transaminases (defined as AST <5 times upper limit of normal)
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E.4 | Principal exclusion criteria |
• Patients with a mean of >20% of the intratrabecular marrow space involved with lymphoma on bone marrow biopsy following induction Rituximab therapy. • Patients with active obstructive hydronephrosis. • Patients with initial disease bulk greater than 10cm. • Patients with evidence of active infection requiring i.v. antibiotics at the time of study entry. • Patients with advanced heart disease or other serious illness that would preclude evaluation. • Patients with large pleural or peritoneal effusions. • Patients with known HIV infection. • Patients who are pregnant or breast-feeding. Male and female patients must agree to use effective contraception for 3 months following 90Y-ibritumomab tiuxetan antibody therapy. • Patients with prior malignancy other than lymphoma, except for adequately-treated skin cancer, cervical cancer in situ, or other cancer for which the patient has been disease-free for 5 years.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy end point in this study will be to evaluate the rate of partial response (PR), complete response (CR) and overall response rate (ORR) according to tumor response criteria according to the “International workshop to standardize response criteria for Non-Hodgkin´s lymphomas”. CR/unconfirmed (CRu) will be categorized as CR.
Secondary end points time to disease progression and response duration for the responders.
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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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | Information not present in EudraCT |
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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After data from first 10 evaluable patients is available an interim analysis will be peformed to medically assess whether the continuation of the trial is justified. All patients followed at least until last patient completed 21 weeks post-Zevalin treatment follow-up. After end of treatment period patients will be followed for disease progression and survivial. LPLV (Last Patient Last Visit) may be more than 5 years before end of 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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |