E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High-risk Smoldering Multiple Myeloma |
|
E.1.1.1 | Medical condition in easily understood language |
Smoldering Multiple Myeloma |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028233 |
E.1.2 | Term | Multiple myeloma without mention of remission |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 the study is to demonstrate that siltuximab will delay progression of high-risk SMM as measured by the 1 year progression-free survival (PFS) rate. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to evaluate additional efficacy measurements including PFS and patient-reported symptoms (patient-reported outcomes [PROs]), as well as safety, pharmacokinetics, antibodies to siltuximab (immunogenicity), and potential biomarkers predictive of response to siltuximab treatment and progression to symptomatic multiple myeloma. Upon progression to multiple myeloma, cytogenetics and response to first subsequent multiple myeloma treatment will be characterized. During an interim analysis, the 6 month progressive disease indicator rate and other endpoints will be evaluated. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of SMM for < 4 years and a diagnosis of high-risk SMM
2. Patients must be within certain limits for protocol-specified laboratory tests
3. Eastern Cooperative Oncology Group Performance Status score of 0 or 1
4. Women of childbearing potential must agree to use adequate birth control measures during the study and for 3 months after receiving the last dose of study agent, and must have a negative pregnancy test at screening
5. Men must agree to use a double-barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study agent. |
|
E.4 | Principal exclusion criteria |
1. Having symptomatic multiple myeloma, defined by any of the
following (if due to myeloma): lytic bone lesions, severe osteopenia (low bone density), pathologic fractures, hypercalcemia (too much calcium in the blood), kidney insufficiency, symptomatic hyperviscosity of the blood, or recurrent serious bacterial infections such as pneumonia
2. Primary systemic AL amyloidosis (a build-up of amyloid light chain proteins in the blood)
3. Prior or concurrent exposure to approved or investigational multiple myeloma treatments. Concurrent treatment with bone-protecting agents (eg, bisphosphonates, denosumab), or steroids are only allowed if given in a stable dose and for a nonmalignant condition. Concurrent treatment with erythropoietin-stimulating agents (ESAs) are not allowed.
4. Prior exposure to agents targeting interleukin 6 (IL 6) or the IL 6 receptor
5. Other malignancy within the past 3 years, except for the following, if treated and not active: basal cell or nonmetastatic (non-spreading) squamous cell carcinoma of the skin, cervical carcinoma or International Federation of Gynecology and Obstetrics Stage 1 carcinoma of the cervix |
|
E.5 End points |
E.5.1 | Primary end point(s) |
One-year progression-free survival rate (PFS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
One year after randomization of last patient |
|
E.5.2 | Secondary end point(s) |
1. Progression-free survivial (PFS)
2. European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC QLQ C30)
3. Brief Pain Inventory (worst pain item)
4. Adverse events
5. Clinical laboratory evaluations
6. PD indicator rate
7. Overall survival |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 4 years after randomization of last patient
2. Up to approximately 4 years after randomization of last patient
3. Up to approximately 4 years after randomization of last patient
4. Up to approximately 4 years after randomization of last patient
5. Up to approximately 4 years after randomization of last patient
6. 6 months after randomization of last patient
7. Approximately 4 years after randomization of last patient |
|
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 | No |
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 |
Australia |
Belgium |
France |
Germany |
Greece |
Israel |
Korea, Republic of |
Spain |
Sweden |
United Kingdom |
|
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
|
The study will end approximately 4 years after randomization of the last subject or when the sponsor decides to stop the study, and include the End of Treatment Visit 4 weeks after the last study agent administration. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |