E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with Relapsed or Refractory, Rituximab Naive or Sensitive Follicular B-cell Non Hodgkin s Lymphoma |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025320 |
|
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 study is to determine whether VELCADE with rituximab provides benefit to subjects with relapsed or refractory, rituximab naive or sensitive follicular B-NHL relative to treatment with rituximab alone, as assessed by prolongation of PFS |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives are to determine the 1 overall response rate-ORR CR CR unconfirmed CRu PR to VELCADE in combination with rituximab according to modified criteria developed by the International Workshop to Standardize Response Criteria for NHL IWRC 2 Overall CR rate CR CRu 3 Duration of response 4 time to progression TTP 5 Overall survival OS rate 6 One-year survival rate. The safety objective is to evaluate the safety and tolerability of VELCADE in combination with rituximab Exploratory objectives are mentioned in the protocol. |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Man or woman and age 18 years or older 2. Diagnosis of follicular B-NHL of the following subtypes WHO classification 1997 FL Grades 1 and 2 . 3. Documented relapse or progression following prior antineoplastic treatment. New lesions or objective evidence of progression of existing lesions must document relapse or progression following the previous therapy. If any prior regimen included rituximab, the subject must have responded CR, CRu, PR , and the TTP from the first dose of rituximab must have been 6 months or more. 4. At least 1 measurable tumor mass greater than 1.5 cm in the longest dimension and greater than 1.0 cm in the short axis that has not been previously irradiated, or has grown since previous irradiation 5. No active central nervous system lymphoma 6. Eastern Cooperative Oncology Group status equal or smaller than 2 7.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. 8. In countries where health authorities have approved the pharmacogenomic testing, subjects or their legally acceptable representatives must have signed a separate informed consent that they agree to participate in the genetic part and protein testing part of the study; participation in the genetic and protein testing component is mandatory for testing described in Section 9.5, but optional for serum protein testing and future testing. 10. 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 before entry and throughout the study; and have a negative serum B-hCG pregnancy test at screening. |
|
E.4 | Principal exclusion criteria |
1. Diagnosed or treated for a malignancy other than NHL within 1 year of randomization, or who were previously diagnosed with a malignancy other than NHL and have any radiographic or biochemical marker evidence of malignancy. Subjects with completely resected basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy are not excluded. 2. Clinical evidence of a transformation from indolent NHL to a more aggressive form of NHL. 3. History of disallowed therapies -Prior treatment with VELCADE -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 -Stem cell transplant within 6 months before randomization -Major surgery within 2 weeks before randomization 4. Residual toxic effects of previous therapy or surgery of Grade 3 or worse 5. Peripheral neuropathy or neuropathic pain of Grade 2 or worse 6. Have received an experimental drug or used an experimental medical device within 21 days before the planned start of treatment. 7. History of allergic reaction attributable to compounds containing boron or mannitol 8. Known anaphylaxis or immunoglobulin E IgE -mediated hypersensitivity to murine proteins or to any component of rituximab including polysorbate 80 and sodium citrate dihydrate 9. Concurrent treatment with another investigational agent 10. Female subject who is pregnant or breast-feeding |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is Progression Free survival which is defined as the interval between the date of randomization and the date of PD or death, whichever is first reported in the intent-to-treat ITT population. Subjects who withdraw from the study i.e., withdrawal of consent, lost to follow-up or change therapy without documented progression will be censored at the time of the last adequate disease assessment. Subjects who complete the study, have not progressed, and are still alive at the cut-off date of the final analysis will be censored at the last adequate disease assessment. Secondary Endpoints please refer to the protocol. |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | 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.8.3 |
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 | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
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 | 4 |