E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 |
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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 primary objective is to determine if the addition of daratumumab to VMP will prolong PFS compared with VMP. |
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E.2.2 | Secondary objectives of the trial |
- To determine if the addition of daratumumab to VMP will improve clinical outcome as measured by:
Time to disease progression (TTP)
Stringent CR (sCR) rate
CR rate
PFS2 (defined as time from randomization to progression on the next line of therapy or death, whichever comes first)
Time to next treatment
Overall response rate (CR + partial response [PR] rate)
Proportion of subjects who achieve very good partial response (VGPR) or better
Duration of response
Overall survival
- To determine the ability of daratumumab to reduce minimal residual disease (MRD)
- To assess patient reported outcomes and heath economic/resource utilization
- To determine the pharmacokinetics and immunogenicity of daratumumab
- To assess the safety and tolerability of daratumumab when administered in combination with VMP
- To evaluate clinical efficacy of daratumumab when added to VMP in high risk molecular subgroups. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participant with documented multiple myeloma satisfying the CRAB criteria and measurable disease
- Participants who are newly diagnosed and not considered candidate for high-dose chemotherapy with stem cell transplantation (SCT) due to: being age >=65 years, or in participants <65 years: presence of important comorbid conditions likely to have a negative impact on tolerability of high dose chemotherapy with
stem cell transplantation
- Participant must have an Eastern Cooperative Oncology Group (ECOG)
performance status score of 0, 1, or 2 - Meet the clinical laboratory criteria as specified in the protocol
- A woman of childbearing potential must have a negative serum pregnancy test at screening within 14 days prior to randomization
- Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device, hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants] or partner’s vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin prior to dosing. Reliable contraception is indicated even where there has been a history of infertility, unless due to
hysterectomy or bilateral oophorectomy |
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E.4 | Principal exclusion criteria |
- Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma
- Participant has a diagnosis of Waldenstrom’s disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
- Participant has prior or current systemic therapy or stem cell transplantation (SCT) for multiple myeloma, with the exception of an emergency use of a short course of corticosteroids before treatment
- Participant has peripheral neuropathy or neuropathic pain Grade 2 or higher,
as defined by the national cancer institute common terminology criteria for adverse events (NCI CTCAE) Version 4
- Participant has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical
monitor, is considered cured with minimal risk of recurrence within 3 years)
- Participant has any concurrent medical or psychiatric condition or disease (example active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free Survival (PFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assess at approximately 41 months from randomization |
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E.5.2 | Secondary end point(s) |
1. Time to DiseaseProgression (TTP)
2. Percentage of Participants Achieving Stringent Complete Response (sCR)
3. Percentage of Participants Achieving Complete Response (CR)
4. Progression-free Survival on Next Line of Therapy (PFS2)
5. Percentage of Participants With Minimal Residual Disease (MRD)
6. Time to Next Treatment
7. Overall Response Rate (ORR)
8. Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better
9. Duration of Response
10. Overall Survival (OS) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- For secondary end points 1-4, 6-9 = Assess at approximately 41 months
from randomization
- For secondary end points 5 = Week 58, 84, and 110
- For secondary end points 10 = Assess at approximately 41 months after first patient randomized up to a maximum of 5 years after last participant is dosed |
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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 | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 129 |
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 |
Argentina |
Australia |
Brazil |
Georgia |
Japan |
North Macedonia |
Russian Federation |
Serbia |
Turkey |
Ukraine |
United States |
Belgium |
Croatia |
Czechia |
Germany |
Greece |
Hungary |
Italy |
Poland |
Portugal |
United Kingdom |
Bulgaria |
Romania |
Spain |
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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
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the following is included in the protocol : The end of the study will occur when 330 subjects have died, or 5 years after the last subject is randomized, whichever comes first. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |