| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Subjects with recurrent advanced follicular lymphoma |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10029547 |
| E.1.2 | Term | Non-Hodgkin's lymphoma |
|
| 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. |
|
| 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 therapy
• To evaluate the safety and tolerability of VELCADE in combination with fludarabine
|
|
| 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 NHL grades 1or 2 according
to the World Health Organization classification
• Subjects must have received at least 12 doses (375 mg/m squared 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
• Absolute neutrophil count (ANC) ≥1.2 x 10 to the ninth cells/L
• Platelets ≥100 x 10 to the ninth cells/L (subjects should not have received platelet
transfusion in the preceding 7 days)
• Alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤2.5 x ULN
• Total bilirubin ≤1.5 x ULN
• Measured or calculated creatinine clearance >70 mL/min
• To participate in the pharmacogenomic component of this study, subjects
(or their legally acceptable representative) must sign 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 β-hCG pregnancy test at
screening
• Subjects (or their legally acceptable representatives) must sign 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 |
|
| 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, ductal carcinoma in situ 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 (and for several months after discontinuation
of therapy) for any signs of active hepatitis infection and treatment
promptly stopped if active hepatitis disease is observed.
• Active central nervous system lymphoma. Brain magnetic resonance
imaging (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. |
|
| 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 response-evaluable subjects 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. The CT scans and other radiographic evaluations will be centrally assessed by an IRC to confirm disease response for the purpose of the efficacy analyses. Additionally, the CT scans or other radiographic evaluations will be locally assessed by a radiologist during the conduct of the study for the purpose of treatment decision-making. |
|
| 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 | Yes |
| 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 | 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| 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 | 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
|
|
| 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 | 3 |
| E.8.9.1 | In the Member State concerned days | 4 |
| 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 | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 4 |
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