E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The subject population comprises adult male and female subjects with multiple myeloma that has relapsed or progressed after prior systemic antineoplastic therapy, presence of measurable secretory disease, Karnofsky performance status score greater than or equal to 70%, and clinical hematology and chemistry laboratory values that meet predefined criteria |
|
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 | 10028228 |
E.1.2 | Term | Multiple myeloma |
|
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 compare the overall response rate ORR (CR+PR), after 4 cycles, of subcutaneously (SC) administered VELCADE® and intravenously (IV) administered VELCADE® in patients with previously treated multiple myeloma. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are: - to determine the CR, nCR and VGPR rates after 4 cycles of single-agent VELCADE®, the ORR after 8 cycles including the effect of adding dexamethasone, the duration of response (DOR), time to disease progression (TTP), progression-free survival (PFS), 1-year survival, and time to response following VELCADE® treatment, administered either SC or IV, - to evaluate the safety and tolerability of the 2 routes of administration, including the local tolerability of SC administration - to describe the plasma pharmacokinetics and pharmacodynamics (via 20S proteasome inhibition assay in whole blood) of SC administered VELCADE® as compared to IV administered VELCADE®
|
|
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 |
For subjects at selected sites, participation in a pharmacokinetic/pharmacodynamic substudy will be mandatory. Approximately 18 subjects per administration route will be enrolled to ensure completion of 12 evaluable subjects per group. |
|
E.3 | Principal inclusion criteria |
Potential subjects must satisfy the following criteria to be enrolled in the study: 1. Male or female subjects 18 years or older 2. Diagnosis of multiple myeloma based on the standard criteria provided in the protocol 3. Measurable, secretory multiple myeloma defined as a serum monoclonal IgG of ≥10 g/L, serum monoclonal IgA, or IgE ≥5 g/L, or serum monoclonal IgD ≥0.5 g/L, or urine M-protein of ≥200 mg/24 hr 4. Relapse or progression of myeloma following prior systemic antineoplastic therapy. Relapse or progression is defined by any of the following: · Reappearance of measurable disease (as defined above) following CR · ≥25% increase in serum or urine M-protein · Development of new or worsening lytic bone disease · New plasmacytomas or ≥50% increase in the longest dimension of an existing plasmacytoma · Worsening hypercalcemia (corrected serum Ca >11.5 mg/dL [2.8 mmol/L]) due to multiple myeloma 5. Karnofsky performance status ≥70% 6. Platelet count ≥50 x 10^9/L without transfusion support within 7 days before the laboratory test 7. Hemoglobin ≥8 g/dL (≥4.96 mmol/L) without transfusion support within 7 days before the laboratory test. 8. Absolute neutrophil count (ANC) ≥0.75 x 10^9/L. 9. Corrected serum Ca <14 mg/dL (<3.5 mmol/L) 10. Aspartate aminotransferase (AST) ≤2.5X upper limit of normal (ULN) 11. Alanine aminotransferase (ALT) ≤2.5X ULN 12. Total bilirubin ≤1.5X ULN (except in subjects with congenital bilirubinemia, such as Gilbert syndrome) 13. Creatinine clearance ≥20 mL/min 14. Toxic effects of previous therapy or surgery have resolved to CTCAE Grade 1 or better 15. Women who are not post-menopausal or surgically sterile must have a negative pregnancy test and agree to use an acceptable method of birth control during the study until 30 days after the last dose of study drug. 16. Men must agree to not father a child and agree to use a latex condom during treatment and for 30 days after the last dose of study drug, even if they have had a successful vasectomy, if their partners are of childbearing potential. 17. Voluntary written informed consent must be given before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
|
|
E.4 | Principal exclusion criteria |
Potential subjects who meet any of the following criteria will be excluded from participating in the study: 1. Previous treatment with VELCADE® 2. More than 3 previous lines of therapy (separate lines of therapy are defined as single or combination therapies that are either separated by disease progression or by a >6 month treatment-free interval) 3. Peripheral neuropathy or neuropathic pain of NCI CTCAE Grade ≥2 4. Any of the following within 3 weeks prior to randomization: antineoplastic or experimental therapy, corticosteroid use above 10 mg/day (prednisone or equivalent), or plasmapheresis 5. Any of the following within 2 weeks prior to randomization: radiation therapy, major surgery (kyphoplasty is not considered major surgery) 6. Prior malignancy other than multiple myeloma diagnosed or treated within the last 2 years, with the exception of completely resected carcinoma in situ or basal/squamous carcinoma of the skin 7. Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or clinically significant conduction system abnormalities 8. Concurrent medical condition or disease (e.g., active systemic infection, uncontrolled diabetes, pericardial disease, acute diffuse infiltrative pulmonary disease, therapeutic use of anticoagulants) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study 9. History of allergic reaction attributable to compounds containing boron or mannitol
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the overall response rate ORR (CR+PR) after 4 cycles (prior to the addition of dexamethasone) for the SC group and the IV group. |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | 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 | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 | 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
| |
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 | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |