E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this study is to evaluate if the addition of daratumumab to Bortezomib, Thalidomide and Dexamethasone will increase the stringent complete response rate after consolidation therapy and increase the progression free survival after daratumumab maintenance therapy in transplant eligible participants with previously untreated Multiple Myeloma. |
|
E.2.2 | Secondary objectives of the trial |
-Progression-free survival (PFS) from first randomization -Time to progression (TTP) -Post-ASCT/ consolidation CR rate -Post-ASCT/consolidation MRD negative rate -Post-induction sCR rate -PFS2 (from first randomization) -OS (from first randomization) |
|
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 |
CASSIO-PET - Version 1 - 24 June 2016: Assessment of the prognostic value of FluoroDeoxyGlucose - Positron Emission Tomography - Computed Tomography (PET-CT) at diagnosis and follow up in patients treated in the Cassiopeia study. Primary Objective: · To compare the PFS of subjects reaching MFC-based MRD negativity and PET-CR 100 days post-ASCT with the PFS of patients not reaching double negativity. Secondary Objectives: · To compare the PFS of patients reaching NGS-based MRD negativity and PET-CR with PFS not reaching double negativity. · To compare PET-CR rate between the two arms of the Cassiopeia study (VTD versus VTD-Dara). · To assess the prognostic value of PET-CR rate in terms of PFS · To assess the prognostic value of PET-CT at diagnosis in terms of PFS · To compare the PFS of patients reaching sCR as defined in Cassiopeia trial and the PET-CR 100 days post-ASCT with the PFS of patients not reaching double negativity
|
|
E.3 | Principal inclusion criteria |
- diagnosis of previously untreated multiple myeloma (MM) - have a confirmed diagnosis and eligible for high dose chemotherapy and autologous stem cell transplantation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
|
|
E.4 | Principal exclusion criteria |
- previous treatment for Multiple Myeloma - Primary amyloidosis, Plasma Cell Leukemia or Smoldering Multiple Myeloma - Prior or concurrent exposure to systemic therapy or SCT for any plasma cell dyscrasia, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment, or received an investigational drug or used an invasive investigational medical device within 4 weeks before Cycle 1, Day 1 - history of malignancy (other than Multiple Myeloma) within 10 years before the date of randomization, except for the following if treated and not active: basal cell or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of breast, or International Federation of Gynecology and Obstetrics (FIGO) Stage 1 carcinoma of the cervix - known chronic obstructive pulmonary disease (COPD) or moderate to severe asthma - any concurrent medical or psychiatric condition or disease (eg, autoimmune disease, active systemic disease, myelodysplasia) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. The percentage of participants who achieve a stringent complete response (sCR) after consolidation therapy 2. The percentage of increase in progression free survival after maintenance therapy |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 9 months for point 1. Up to 60 months for point 2. |
|
E.5.2 | Secondary end point(s) |
1. PFS (from first randomization) 2.Time to progression (TTP) 3.Post-ASCT/ consolidation CR rate 4.Post-ASCT/consolidation MRD negative rate 5.Post-induction sCR rate 6.PFS2 (from first randomization) 7.OS (from first randomization) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
points 1, 2, 6, 7 - Up to 60 months points 3, 4 - Up to 9 months point 5 - Up to 4 months |
|
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 | 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 | No |
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 | 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.8.2.4 | 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 | 29 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 115 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
The end of the study will occur approximately 5 years after the last participant is randomized in the second phase of the study. Refer to protocol. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 9 |
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 | 9 |
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 |