| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Multiple Myeloma |
| Mieloma Multiplo |
|
| E.1.1.1 | Medical condition in easily understood language |
| Multiple Myeloma |
| Mieloma Multiplo |
|
| 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 | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare the efficacy of Tec-Dara with DPd/DVd |
| confrontare l'efficacia dell'associazione teclistamab/daratumumab con DPd/DVd |
|
| E.2.2 | Secondary objectives of the trial |
- To further compare the efficacy of Tec-Dara with DPd/DVd
- To assess the safety profile of Tec-Dara
- To characterize the PK of teclistamab
- To assess the immunogenicity of teclistamab and daratumumab
- To compare the patient-reported outcomes (PROs) of Tec-Dara with DPd/DVd
- To evaluate the efficacy of teclistamab in-high-risk molecular subgroups |
confrontare l'efficacia dell'associazione teclistamab/daratumumab con la terapia DPd/DVd
valutato il profilo di sicurezza dell'associazione teclistamab daratumumab
caratterizzare la PK di teclistamab
valutare l'immunogenicità di teclistamab e di daratumumab
confrontare i patient reported outcome (PRO) dell'associazione teclistamab/daratumumab e DPd/DVd
valutare l'efficacia di teclistamab nei sottogruppi molecolari ad alto rischio |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. =18 years of age.
2. Documented multiple myeloma as defined by the criteria below:
a. Multiple myeloma diagnosis according to the IMWG diagnostic criteria
b. Measurable disease at screening as defined by any of the following:
1) Serum M-protein level =0.5 g/dL (central laboratory); or
2) Urine M-protein level =200 mg/24 hours (central laboratory); or
3) Serum immunoglobulin free light chain =10 mg/dL (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain ratio.
3. Received 1 to 3 prior line(s) of antimyeloma therapy (Appendix 6) including a PI and lenalidomide.
a. Participants who have received only 1 line of prior line of antimyeloma therapy must be lenalidomide refractory (ie, have demonstrated progressive disease by IMWG criteria during treatment or within 60 days
of completion of lenalidomide-containing regimen). Progression on orwithin 60 days of the last dose of lenalidomide given as maintenance will meet this criterion.
4. Documented evidence of progressive disease based on investigator's determination of response by IMWG criteria on or after their last regimen.
5. Have an ECOG performance status score of 0, 1, or 2 at screening and immediately prior to the start of administration of study treatment (Appendix 7).
6. Have clinical laboratory values meeting the following criteria during the Screening Phase. In addition, these laboratory values must be reevaluated within the 72 hours prior to the first dose and the participant must also meet all criteria. If one or more criteria are not met 72 hours prior to dosing, one repeat of laboratory testing is permitted. If >1 repeat laboratory test is necessary, the sponsor must be consulted prior to dosing
7. A woman of childbearing potential must have a negative highlysensitive serum pregnancy test at screening and again within 24 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study
8. A woman must be:
a. Not of childbearing potential, or
b. Of childbearing potential and
1) Practicing true abstinence; or
2) Have a sole partner who is vasectomized; or
3) Practicing =2 methods of contraception (at least 1 highly effective). For participants who are of childbearing potential and treated with DPd in Arm B, see Section 6.12.3 for details regarding concomitant use of estrogen-containing products and pomalidomide.
9. A woman must agree not to donate eggs (ova, oocytes) or freeze for future use, for the purposes of assisted reproduction during the study and for 90 days after receiving the last dose of study treatment
10. A man must wear a condom (with or without spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 90 days after receiving the last dose of study treatment. If a female partner is of childbearing potential, she must also be practicing a highly effective method of contraception.
11. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study treatment.
12. Must be willing and able to adhere to the lifestyle restrictions specified in this protocol (Section 5.3)
13. Must sign an ICF (or their legally acceptable representative must sign) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study. |
1 maggiore età
2mieloma multiplo così definito:
a diagnosi secondo i criteri del IMWG
b. malattia misurabile allo screening così definita: 1) proteina sierica M =0.5 g/dL o 2) proteina M secreta nellèurina =200 mg/24 hours o3) immunoglobulina libera sierca a catena leggera =10 mg/dL
3 deve aver ricevuto da 1 a 3 linee di trattamento inclusa un PI e la lenalidomide
4) progressione di patologia documentata in base ai criteri IMWG
5) performance ECOG 0 1 o 2 allo screening e subito prima della somministrazione del farmaco di studio
6) valori di laopratorio concordi con i seguenti criteri; in aggiunta, i test devono essere rieffettuati entro 72 ore prima della prima dose e i partecipanti devono rispettare tutti i criteri. se uno o più criteri non sono rspettati entro le 72 ore precedenti, si può rifare un test di laboratorio. se dev'essere ripetuto più di un test, lo sponsor dev'essere consultato prima cheil trattamento sia somministrato.
7) una donna in età fertile deve avere un test di gravidanza su siero negativo, allo screening e entro 24 ore dall'inizio del trattamento di studio, e deve acconsentire a farne altri durante lo studio
8) una donna deve essere in età non fertile o deve praticare astinenza, o avere un solo partner vasectomizzato, o utilizzare almeno 2 metodi metodi di contraccezione (di cui almeno 1 altamente efficaci)
9) una donna non deve donare ovuli per la durata dello studio e nei 90 giorni successivi alla fine
10) un'uomo deve utilizzare preservativi, durante il trattamento e fino a 90 giorni dopo
11) un uomo non deve donare sperma per la durata dello studio e nei 90 giorni successivi alla fine
12) deve volontariamente aderire allo stile di vita richiesto dallo studio
13) deve firmare un consenso informato (o il rappresentante legale deve farlo per loro), indicando che lo scopo della ricerca viene compreso |
|
| E.4 | Principal exclusion criteria |
1 Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the teclistamab Investigator's Brochure and appropriate package inserts), Additional exclusion criteria pertaining to specific study drugs include:
a. A participant is not eligible to receive DPd as control therapy if any of the following are present:
1) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to pomalidomide
2) Disease that is considered refractory to pomalidomide per IMWG (progression during treatment or within 60 days of completing treatment with pomalidomide).
b. A participant is not eligible to receive DVd as control therapy if any of the following are present:
1) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to bortezomib (intolerance defined as prior therapy discontinued due to any AE related to bortezomib)
2) Grade 1 peripheral neuropathy with pain or Grade =2 peripheral neuropathy as defined by NCI-CTCAE Version 5.0
3) Disease that is considered refractory to bortezomib per IMWG
4) Received a strong CYP3A4 inducer (see Section 6.12.3.3) within 5 half-lives prior to randomization.
c. A participant is not eligible for this study if they are refractory to both pomalidomide and bortezomib.
2. Received any prior BCMA-directed therapy.
3. Has disease that is considered refractory to an anti-CD38 monoclonal antibody per IMWG (progression during treatment or within 60 days of completing therapy with an anti-CD38 monoclonal antibody).
4. Received the following prior antimyeloma therapy, in the specified time frame prior to randomization:
a. Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or =5 half-lives, whichever is less
b. Investigational vaccine within 4 weeks
c. Monoclonal antibody therapy within 21 days
d. Cytotoxic therapy within 21 days
e. PI therapy within 14 days
f. IMiD agent therapy within 14 days
g. Radiotherapy within 14 days or focal radiation within 7 days
h. Gene-modified adoptive cell therapy within 3 months.
5. Stem cell transplant:
a. An allogeneic stem cell transplant within 6 months before randomization. in case, the pts must be off all immunosuppressive medications for =42 days without signs of graft-versus-host disease before randomization.
b. An autologous stem cell transplant within 12 weeks before randomization.
6. Received a cumulative dose of corticosteroids equivalent to =140 mg of prednisone within 14 days before randomization.
7. Received a live, attenuated vaccine within 4 weeks before randomization.
8. Myelodysplastic syndrome or active malignancies other than relapsed/refractory multiple myeloma. The only allowed exceptions are:
a. Non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured
b. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured
c. Noninvasive cervical cancer treated within the last 24 months that is considered completely cured
d. Localized prostate cancer (N0M0):
1) With a Gleason score of =6, treated within the last 24 months, or untreated and under surveillance
2) With a Gleason score of 3+4 that has been treated >6 months prior to full study screening and considered to have a very low risk of recurrence, or
3) History of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence.
e. Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence
f. Other malignancy that is considered cured with minimal risk of recurrence.
9. Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome, or primary amyloid light chain amyloidosis. |
1. controindicazioni quali allergie gravi, ipersensibilità o intolleranza ai farmaci o agli eccipienti;
A) un paziente non è eleggibile per terapia con DPd se:
1 esistono contronindicazioni quali allergie gravi, ipersensibilità o intolleranza;
2 la malattia è refrattaria al trattamento con pomalidomide in base ai criteri IMWG
B) un paziente non è eliggibile alla terapia con DVd se:
1 esistono controindicazioni quali allergie gravi, ipersensibilità o intolleranza;
2 c'è una neuropatia periferica di grado 1 con dolore o di grado 2 definita dai criteri NCI-CTCAE v5.0
3 la malattia è refrattaria al Bortezomib seocndo i criteri IMWG
4 ha ricevuto un forte induttore del CYP3A4 entro 5 emivite prima della randomizzazione
C) un partecipante non è eleggibile per questo studio se sono refrattari sia al pomalidomide che al bortezomib
2 ha ricevuto una terapia contro BCMA
3 ha delle malattie che sono considerate refrattarie agli anticorpi monolconali anti CD38 in base ai crtieri IMWG
4 ha ricevuto una qualsiasi precedente terapia antimieloma, in un periodo di tempo specifico prima della randomizzazione
a: terapia target, terapia epigenetica, trattamento con farmaci sperimentali o con dispositivi medici sperimentali invasivi entro 21 gg o 5 emivite del farmaco
b vaccini sperimentali entro 4 settimane
c. terapia monoclonale entro 21 gg
d terapia citotossica entro 21 gg
e terapia PI entro 14 gg
f terapia con agenti IMiDentro 14 gg
g radioterapia entro 14 gg o radiazione focale entro 7 gg
h cellule ingegnerizzate entro 3 mesi
5.trapianto di cellule staminali:
a trapianto di cellule allogeniche staminali entro 6 mesi; in caso, il paziente deve aver smesso le terapie immunospprressive entro 42 gg senza segni di patologie da innesto prima della randomizzazione
b trapianto di cellule staminali autologhe entro 12 settimane prima della randomizzazione
6 non deve aver rcevuto una dose comulativa di corticosteroidi fino a 140mg di prednisone entro 14gg
7 non deve aver recrvuto un vaccino vivo attenuato entro 4 settimane
8 non deve avere sindrome mielodisplastica o altri tumori maligni attivi, a meno che non sia un mieloma multiplo refrattario. le uniche eccezioni sono:
a. tumore alla vescica non invasivo, entro 24 mesi e curato
b. tumore alla pelle trattato entro 24 mesi e curato
c tumore alla cervice uterina trattato entro 24 mesi e curato
d. tumore alla prostata localizzato (N0M0):
1 con punteggio Gleason =6, trattato da 24 mesi non trattato
2 con punteggio Gleason 3o4, trattato entro 6 mesi prima dello screening e con rischio di recidiva molto basso
3 storia di tumore alla prostata localizzato trattato con terapia androgeno deprivante
e tumore al seno, tumore loculare trattato o duttale trattato; storia di tumore localizzato al senso trattato con agenti antiormonali
f. altri tumori maligni
9 leucemia delle plasmacellule, macroglobulinemia di Waldestrom, sindrome POEMS, amiloidosi a catena leggera primaria |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| PFS |
| sopravvivenza senza progressione di patologie |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| dosing day |
| il giorno della somministrazione |
|
| E.5.2 | Secondary end point(s) |
- Overall response (PR or better)
- VGPR or better
- CR or better
- MRD negativity
- PFS-2
- OS
- Time to next treatment |
risposta globale
VGPR
CR
negatività MRD
PFS-2
OS |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| dosing day |
| il giorno della somministrazione |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| 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) | 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 | 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) | 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 61 |
| 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 | Information not present in EudraCT |
| 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 |
| Brazil |
| Canada |
| China |
| Japan |
| Korea, Republic of |
| Russian Federation |
| Taiwan |
| Ukraine |
| United States |
|
| 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
|
| Final OS analysis |
| analisi finale della sopravvivenza globale |
|
| 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 | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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