|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Diseases [C] - Blood and lymphatic diseases [C15]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|Condition being studied is a rare disease
|E.2 Objective of the trial
|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.
|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.
|Trial contains a sub-study
|Principal inclusion criteria
|Each patient must meet all the following inclusion criteria to be enrolled in the study:
1. At least 18 years of age, with at least 6 months expected survival.
2. Prior confirmed diagnosis of multiple myeloma (2014) (16).
3.Received standard first line treatment with at least a very good partial response (VGPR), according to IMWGs criteria . Standard first line treatment is defined as
VRD, VTD or VCD followed by ASCT with or without lenalidomide maintenance initiated (Patients where the monoclonal component or dFLC increases during the period from best response to screening can be included if there is no progressive disease.)
4.Patients must be carfilzomib naïve.
5.A positive PET-CT result from central reviewer in the screening period
6. Successful FISH evaluation performed with available results
7. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that the patient may withdraw consent at any time without prejudice to future medical care.
8. Females of childbearing potential (FCBPs) must have a confirmed negative serum pregnancy test within the 7 days prior to inclusion
9.of contraceptive during the study and for 30 days following the last study drug dose. Male subjects must use contraception and refrain from donating sperm for at least 90 days after the last dose of carfilzomib.
10. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. In patients >75 years of age, performance status 0-1.
11.Patients must meet the following adequate organ and bone marrow function within 21 days prior to inclusion:
Absolute neutrophil count (ANC) ≥ 0,5 x 109/L) and platelet count 35 x 109/L. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. Granulocyte growth factors are allowed to meet the inclusion criteria.
12. Patient must be willing and able to adhere to the study schedule and other protocol requirements.
|Principal exclusion criteria
|1. Change of first line treatment because of stable or progressive disease.
2. Female patients who are lactating or have a positive serum pregnancy test during the screening period.
3. Major surgery within 28 days before enrollment.
4. Radiotherapy within 14 days before enrollment. Glucocorticoid therapy within the 14 days prior to inclusion that exceeds a cumulative dose of 160 mg dexamethasone or 1000 mg prednisone.
5. Patients who started treatment more than 12 month before screening
6. Central nervous system involvement.
7. 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
8. Active hepatitis B or C infection or known human immunodeficiency virus (HIV) positivity.
9. Any other serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.
10. Known allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib) or to any of the study medications, their analogues, or excipients in the various formulations of any agent.
11. Contraindication to dexamethasone or any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment.
12. 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.
13. Patients that have previously been treated with carfilzomib.
14. Primary plasma cell leukemia, systemic AL amyloidosis, Waldenströms macroglobulinemia, POEMS syndrome.
15. Pleural effusions requiring thoracocentesis within the 14 days prior the inclusion.
16. Ascites requiring ascites puncture within the 14 days prior to inclusion.
17. Previous allogeneic transplantation
18. Uncontrolled hypertension or uncontrolled diabetes despite medication
19. Contraindication to PET-CT
20. Not expected to tolerate full dose KRd
|E.5 End points
|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.
|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.
|Secondary end point(s)
|- MRD negativitiy by 8-colour Euroflow after 4 cycles of KRd consolidation
- Overall response rate
- Progression-free survival (PFS)
- Time to next treatment (TTNT)
- Overall survival (OS)
- Quality of life during and after KRd consolidation
|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.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|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.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years