E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059433 |
E.1.2 | Term | Follicular mixed small and large cell lymphoma recurrent |
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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 |
The primary objective is to determine the complete response rate (CR+CRu) following treatment with VELCADE in combination with fludarabine (VF) compared with rituximab in combination with fludarabine (RF) in subjects with recurrent advanced follicular lymphoma. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are as follows: To determine the overall response rate (CR+CRu+PR) To determine the duration of response To determine time to progression (TTP) To determine progression-free survival (PFS) To determine overall survival (OS) To determine the time to subsequent anti-lymphoma thera |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Potential subjects must satisfy the following criteria to be enrolled in the study: Male or female subjects 18 years or older Histologically proven diagnosis of follicular non-Hodgkin�s lymphoma grades 1or 2 according to the World Health Organization classification 41 Subjects must have received at least 14 doses (375mg/m2 or appropriately adjusted dose) of rituximab for the treatment of this lymphoma as single agent rituximab or in rituximab-containing regimens as documented in the subject�s medical record Documented relapse or progression following last antineoplastic treatment At least 1 measurable tumor mass (>=1.5 cm x >=1.0 cm) Eastern Cooperative Oncology Group [ECOG] performance status =<2 (Attachment 1) Absolute neutrophil count (ANC) >=1.2 x 109 cells/L Platelets >=100 x 109 cells/L (subjects should not have received platelet transfusion in the preceding 7 days) Alanine aminotransferase =<2.5 x upper limit of normal (ULN) Aspartate aminotransferase =<2.5 x ULN Total bilirubin =<1.5 x ULN Measured or calculated creatinine clearance >70 mL/min (see Attachment 2 for the Cockcroft-Gault formula ) To participate in the pharmacogenomic component of this study, subjects (or their legally acceptable representative) must have signed the informed consent form for pharmacogenomic research indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit) Female subjects must be postmenopausal (for at least 6 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and have a negative serum beta-hCG pregnancy test at screening Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study |
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E.4 | Principal exclusion criteria |
Potential subjects who meet any of the following criteria will be excluded from participating in the study: Subjects with histological or clinical transformation to an aggressive lymphoma History of disallowed therapies: prior treatment with VELCADE or fludarabine. antineoplastic (including unconjugated therapeutic antibodies), experimental, or radiation therapy within 3 weeks before randomization nitrosoureas within 6 weeks before randomization radioimmunoconjugates or toxin immunoconjugates within 10 weeks before randomization major surgery within 3 weeks before randomization chronic use of corticosteroids, such as dexamethasone Note: Prednisone =<15 mg per day or its equivalent is allowed Peripheral neuropathy or neuropathic pain of Grade 2 or worse Diagnosed or treated for a malignancy other than NHL except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, DCIS of the breast, or other solid tumors curatively treated with no evidence of disease for >5 years Active systemic infection requiring treatment. Hepatitis carriers are not excluded from this study. However, hepatitis carriers should be carefully monitored during treatment for any signs of active hepatitis infection and treatment promptly stopped if active hepatitis disease is observed. Active central nervous system lymphoma. Brain MRI is required only if clinically indicated Recently received (within the past 6 months) a live virus vaccine History of allergic reaction attributable to compounds containing boron, mannitol, rituximab, or similar agents Serious medical conditions (such as severe hepatic impairment, pericardial disease, acute diffuse infiltrative pulmonary disease, systemic infections, etc) or psychiatric illness likely to interfere with participation in this clinical study Concurrent treatment with another investigational agent. Concurrent participation in non-treatment studies is not excluded. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the complete response rate, which is defined as the proportion of responsee valuable subjects (see Section 11.1 for definition of study populations) who achieve a confirmed CR or CRu. Disease response and progression will be evaluated according to modified IWRC criteria by radiographic imaging and other procedures as necessary. |
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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 | Yes |
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 | 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) | Yes |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |