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] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 |
To assess the proportion of patients that are PET-positive after standard first line treatment, and how many of these can become PET-negative after 4 cycles of KRd (Kyprolis-Revlimid-dexamethasone) consolidation.
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E.2.2 | Secondary objectives of the trial |
The correspondence between PET-CT results and MRD dynamics by intra-patient comparison. Evaluating safety, quality of life and efficacy of KRd consolidation in this population.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Prior confirmed diagnosis of multiple myeloma (2014).
2. Received standard first line treatment with at least very good partial response (VGPR). Standard first line treatment is defined as
- VRD, VTD or VCD followed by ASCT, or
- MPV at least 6 cycles, or no further reduction in monoclonal component the last 2 cycles, or
- Rd at least 9 cycles or no further reduction in monoclonal component the last 2 cycles.
3. Carfilzomib naïve.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
5. Absolute neutrophil count (ANC) ≥ 0,5 x 109/L) and platelet count >35 x 109/L.
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E.4 | Principal exclusion criteria |
1. Change of first line treatment because of stabile or progressive disease.
2. Major surgery within 28 days before enrollment.
3. Radiotherapy within 14 days before enrollment, but if the involved field is small, 7 days will be considered a sufficient interval before onset of the treatment.
4. Glucocorticoid therapy within the 14 days prior to inclusion that exceeds a cumulative dose of 160 mg dexamethasone or 1000 mg prednisone.
5. Central nervous system involvement.
6. Uncontrolled heart disease, including congestive heart failure (NYHA III-IV), uncontrolled angina pectoris, uncontrolled conduction abnormalities, acute diffuse infiltrative pulmonary disease, pericardial disease or myocardial infarction within 6 months prior to enrollment
7. Uncontrolled hypertension or uncontrolled diabetes despite medication
8. Active hepatitis B or C infection or known human immunodeficiency virus (HIV) positivity.
9. Another active malignancy. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
10. Primary plasma cell leukemia, systemic AL amyloidosis, Waldenströms macroglobulinemia, IgM multiple myeloma, POEMS syndrome, myelodysplastic syndrome.
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of PET-CT positivity after standard first line treatment, and change from PET-CT positivity to PET-CT negativity after 4 cycles of KRd consolidation. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PET-CT will be performed at screening to assess the proportion of patients that are PET-positive after standard first line treatment.
Thereafter, PET-CT will be performed one month after completion of study treatment, to assess the number of PET-negative patients after 4 cycles of KRd consolidation. |
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E.5.2 | Secondary end point(s) |
- MRD negativitiy by 8-colour Euroflow after 4 cycles of KRd consolidation
- Safety
- Overall response rate
- Progression-free survival (PFS)
- Time to next treatment (TTNT)
- Overall survival (OS)
- Quality of life during and after KRd consolidation |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- MRD negativity will be evaluated one month after completed consolidation treatment.
- Safety will be followed from study start until 60 days after completed KRd consolidation treatment
- Overall response rate, progression-free survival, time to next treatment, overall survival and quality of lite will be followed throughout the study. After progressive disease the patients will be followed by telephone for overall survival. Patients with negative PET-CT results will be followed by telephone for progression-free survival and overall survival. |
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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 | 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 | 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) | 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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | 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
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Patients will be followed at study visits until progressive disease and thereafter the patients will be followed by telephone until death. Patients with negative PET-CT results will be followed by telephone for progressive-free survival and overall survival. |
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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 | 10 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 10 |