Inobrodib, Pomalidomide and Dexamethasone Versus Standard Available Therapy in Relapsed or Refractory Multiple Myeloma (DOMMINO-2)
17. srpna 2026 aktualizováno: CellCentric Ltd.
A Phase 3, Multicenter, Open-Label, Randomized Study to Evaluate Inobrodib in Combination With Pomalidomide and Dexamethasone Versus Standard Available Therapy in Patients With Relapsed or Refractory Multiple Myeloma
The main purpose of this study is to find out whether inobrodib, when given with pomalidomide and dexamethasone, works better than standard treatment for people whose multiple myeloma has come back or has not improved after previous treatment. The study will look at how long people taking part in the study ("Participants") live without their myeloma getting worse, and how many people's myeloma improves (responds) following treatment.
The study will also look at how long participants live overall, how quickly treatment works, how long the response lasts, whether very small amounts of myeloma can still be found after a good response, quality of life, side effects, and the amount of inobrodib in the blood.
Participants receive treatment in 28-day cycles. One group receives inobrodib by mouth twice a day for 4 days, followed by 3 days without inobrodib each week; pomalidomide by mouth once a day on Days 1 to 21 of each cycle; and dexamethasone once each week.
The other group receives 1 standard treatment chosen by the study doctor from the following treatment options: daratumumab, pomalidomide, and dexamethasone; elotuzumab, pomalidomide, and dexamethasone; or carfilzomib and dexamethasone. Some standard treatments are given by injection or infusion at the study site. Other medicines, such as tablets or capsules, may be taken by mouth as instructed by the study team.
Study checks include questions about symptoms and side effects, review of other medicines, physical checks, blood pressure and other vital sign checks, heart tracing tests, blood and urine tests, scans where needed, bone marrow samples, and questionnaires about symptoms and daily life. Participants in the inobrodib group will have extra blood samples to measure the amount of inobrodib in the blood. Some participants may also have extra research blood samples at selected visits.
Přehled studie
Postavení
Postavení
Nábor
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Detailní popis
This is a Phase 3, multicenter, open-label, randomized study to evaluate inobrodib in combination with pomalidomide and dexamethasone (InoPd) versus standard available therapy (SAT), defined as Investigator's choice of daratumumab or elotuzumab in combination with pomalidomide and dexamethasone (DPd and EPd, respectively) or carfilzomib in combination with dexamethasone (Kd), in participants with relapsed or refractory multiple myeloma (RRMM).
Participants must be 18 years or older and have received 1 to 4 prior lines of therapy only.
Approximately 450 participants will be randomized 1:1 to be treated with either InoPd (Arm A) or Investigator's choice of SAT (Arm B), which includes DPd, EPd and Kd.
Study treatment should be continued until disease progression, initiation of new anticancer therapy, unacceptable toxicity or the participant meets any criteria for withdrawal from the study.
The dual primary objectives are to compare the efficacy of InoPd with Investigator's choice of SAT in terms of progression-free survival (PFS) and objective response rate (ORR) by Blinded Independent Central Review (BICR) in participants receiving InoPd versus participants receiving SAT.
The study will use a Steering Committee, consisting of selected participating Principal Investigators, Contract Research Organization (CRO) and Sponsor representatives, and an Independent Data Monitoring Committee (IDMC), for the purposes of conduct and oversight of the study.
Typ studie
Typ studie
Intervenční
Zápis (Odhadovaný)
Zápis
450
Fáze
Fáze
- Fáze 3
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní kontakt
Studijní kontakt
- Jméno: CCS1477-05 Clinical Operations
- Telefonní číslo: +44 1799 531130
- E-mail: DOMMINO-2@cellcentric.com
Studijní místa
-
-
Florida
-
Miami, Florida, Spojené státy, 33126
- Nábor
- Regis Clinical Research
-
-
Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Ne
Popis
Inclusion Criteria:
- Adults aged 18 years or older (or the minimum age of consent under local rules, if that is 18 or over)
- A diagnosis of multiple myeloma that has either come back (relapsed) or did not respond (refractory) after the most recent treatment
- Myeloma that can be measured using standard study tests (blood and/or urine tests)
- Between 1 and 4 previous courses (lines) of myeloma treatment, which must have included both a treatment that targets CD38 (such as daratumumab or isatuximab) and lenalidomide
- Well enough to carry out daily activities with little or no help (Eastern Cooperative Oncology Group [ECOG] performance status of 0 to 2)
- Suitable blood test results and adequate kidney and liver function
- Willingness to use highly effective contraceptive measures (if sexually active) with all sexual partners
Exclusion Criteria:
- Recent anticancer treatment before starting study treatment: any experimental medicine, chemotherapy, immunotherapy or other anticancer treatment within 14 days or 5 half-lives (whichever is shorter), or certain antibody-based treatments within longer set periods
- Previous treatment with a medicine that works in the same way as inobrodib (a p300/CBP bromodomain inhibitor)
- Myeloma that has already stopped responding to pomalidomide (pomalidomide-refractory), unless only short-term pomalidomide was used and the study doctor confirms the person still meets the study rules
- Unable to receive at least one of the standard treatment options offered in the study, or unable/unwilling to follow the requirements for at least one of those options
- Taking medicines, herbal supplements or foods (for example, strong CYP3A4 inducers or inhibitors) that would interfere with the study treatment
- Major surgery within 4 weeks before the first dose of study treatment
- A live vaccine within 4 weeks before study treatment
- A recent stem cell transplant, or ongoing transplant-related problems such as graft-versus-host disease
- Myeloma affecting the brain, spinal fluid or spinal cord, or ongoing pressure on the spinal cord
- Another active cancer (progressing or needing a change in treatment) in the last 24 months, other than multiple myeloma, apart from certain low-risk or fully treated cancers
- Serious or uncontrolled medical problems, such as uncontrolled heart, lung, liver, bleeding or diabetes conditions, uncontrolled high blood pressure, or a heart-rhythm problem (including QT prolongation)
- An active or uncontrolled infection, including certain cases of HIV, hepatitis B or hepatitis C
- Digestive problems that could stop the study medicines being swallowed or properly absorbed
- Pregnant or breastfeeding, or planning to become pregnant, father a child or donate sperm during treatment or the required post-treatment period
- Any illness or medical history that could affect safety, the ability to follow study requirements, or the interpretation of study results
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Počet zbraní
2
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
|---|---|
|
Experimentální: InoPd
Inobrodib in combination with pomalidomide and dexamethasone
|
Inobrodib in combination with pomalidomide and dexamethasone.
Inobrodib 20 mg orally (PO) twice daily (b.i.d.), 4 days on/3 days off.
Pomalidomide 4 mg PO once daily (o.d.) on Days 1 to 21 of each 28-day cycle.
Dexamethasone 40 mg PO every week (q1w) (20 mg if >75 years old) on Days 1, 8, 15 and 22 of each 28-day cycle.
Treatment will continue until progressive disease, death, unacceptable side effects, withdrawal of consent or end of study, whichever occurs first.
Ostatní jména:
|
|
Aktivní komparátor: Investigator's choice of Standard Available Therapy
Investigator's choice of elotuzumab in combination with pomalidomide and dexamethasone (EPd), daratumumab in combination with pomalidomide and dexamethasone (DPd), or carfilzomib in combination with dexamethasone (Kd).
|
Investigator's choice of elotuzumab in combination with pomalidomide and dexamethasone (EPd), daratumumab in combination with pomalidomide and dexamethasone (DPd), or carfilzomib in combination with dexamethasone (Kd).
Treatment will continue until progressive disease, death, unacceptable side effects, withdrawal of consent or end of study, whichever occurs first.
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Progression-free Survival (PFS) assessed by Blinded Independent Central Review (BICR)
Časové okno: From randomization until progressive disease or death, assessed every 28 days and followed until the final PFS analysis after approximately 330 PFS events; estimated up to approximately 38 months after the start of enrollment
|
Defined as the time from randomization until the earliest date of PD based on International Myeloma Working Group (IMWG) criteria assessed by BICR, or death due to any cause
|
From randomization until progressive disease or death, assessed every 28 days and followed until the final PFS analysis after approximately 330 PFS events; estimated up to approximately 38 months after the start of enrollment
|
|
Objective Response Rate (ORR) assessed by BICR
Časové okno: From randomization until confirmed progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or the ORR data cutoff, whichever occurs first; disease response assessed every 28 days (up to 48 months)
|
Defined as the percentage of participants with a confirmed PR or better, based on IMWG criteria assessed by BICR
|
From randomization until confirmed progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or the ORR data cutoff, whichever occurs first; disease response assessed every 28 days (up to 48 months)
|
Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Overall Survival (OS)
Časové okno: From randomization until death from any cause or the final OS analysis after approximately 329 deaths; survival status assessed every 12 weeks after disease progression or treatment discontinuation (up to 48 months)
|
Defined as the time from randomization to the date of death due to any cause
|
From randomization until death from any cause or the final OS analysis after approximately 329 deaths; survival status assessed every 12 weeks after disease progression or treatment discontinuation (up to 48 months)
|
|
PFS Assessed by the Investigator
Časové okno: From randomization until progressive disease or death; disease assessments performed every 28 days until confirmed progression, death, withdrawal, loss to follow-up, or end of study (up to 48 months)
|
Defined as the time from randomization to the earliest occurrence of progressive disease, as determined by the Investigator according to IMWG response criteria, or death from any cause.
|
From randomization until progressive disease or death; disease assessments performed every 28 days until confirmed progression, death, withdrawal, loss to follow-up, or end of study (up to 48 months)
|
|
ORR Assessed by the Investigator
Časové okno: From randomization until confirmed progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
|
Percentage of participants with a confirmed PR or better as determined by the Investigator according to IMWG response criteria
|
From randomization until confirmed progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
|
|
Minimal Residual Disease (MRD) Negativity Rate
Časové okno: At confirmed CR or better; if MRD negativity is not demonstrated at CR, reassessed within 3 to 6 months after confirmation of CR or better (up to 48 months)
|
Percentage of participants achieving minimal residual disease (MRD) negativity at CR or better, measured by next-generation sequencing
|
At confirmed CR or better; if MRD negativity is not demonstrated at CR, reassessed within 3 to 6 months after confirmation of CR or better (up to 48 months)
|
|
Duration of Response (DoR) Assessed by BICR
Časové okno: From the first documented confirmed response until progressive disease or death; assessed every 28 days until progression or end of study (up to 48 months)
|
Defined, among participants with a confirmed PR or better, as the time from the first documented response to progressive disease determined by BICR or death from any cause, whichever occurs first
|
From the first documented confirmed response until progressive disease or death; assessed every 28 days until progression or end of study (up to 48 months)
|
|
DoR Assessed by the Investigator
Časové okno: From the first documented confirmed response until progressive disease or death; assessed every 28 days until progression or end of study (up to 48 months)
|
Defined, among participants with a confirmed PR or better, as the time from the first documented response to progressive disease determined by the Investigator or death from any cause, whichever occurs first
|
From the first documented confirmed response until progressive disease or death; assessed every 28 days until progression or end of study (up to 48 months)
|
|
Time to Response (TTR) Assessed by BICR
Časové okno: From randomization to the first documented confirmed response; assessed every 28 days (up to 48 months)
|
Defined, among participants achieving a confirmed response, as the time from randomization to the first documented PR or better determined by BICR according to IMWG response criteria
|
From randomization to the first documented confirmed response; assessed every 28 days (up to 48 months)
|
|
TTR Assessed by the Investigator
Časové okno: From randomization to the first documented confirmed response; assessed every 28 days (up to 48 months)
|
Defined, among participants achieving a confirmed response, as the time from randomization to the first documented PR or better determined by the Investigator according to IMWG response criteria
|
From randomization to the first documented confirmed response; assessed every 28 days (up to 48 months)
|
|
Very Good Partial Response (VGPR) or Better Rate Assessed by BICR
Časové okno: From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
|
Percentage of participants with a confirmed VGPR or better-VGPR, CR, or sCR-as determined by BICR according to IMWG response criteria
|
From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
|
|
VGPR or Better Rate Assessed by the Investigator
Časové okno: From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
|
Percentage of participants with a confirmed VGPR or better as determined by the Investigator according to IMWG response criteria
|
From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
|
|
Complete Response (CR) or Better Rate Assessed by BICR
Časové okno: From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
|
Percentage of participants with a confirmed CR or sCR as determined by BICR according to IMWG response criteria
|
From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
|
|
CR or Better Rate Assessed by the Investigator
Časové okno: From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
|
Percentage of participants with a confirmed CR or sCR as determined by the Investigator according to IMWG response criteria
|
From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months)
|
|
Change From Baseline in EORTC QLQ-C30 Scores
Časové okno: Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
|
Defined as the change from baseline in functional, symptom, and global health status/quality-of-life scores from the EORTC QLQ-C30 questionnaire
|
Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
|
|
Change From Baseline in EORTC QLQ-MY20 Disease Symptoms Score
Časové okno: Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
|
Defined as the change from baseline in the Disease Symptoms domain score of the EORTC QLQ-MY20 questionnaire
|
Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
|
|
Change From Baseline in EQ-5D-5L Health Status
Časové okno: Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
|
Defined as the change from baseline in the EQ-5D-5L health-state index and visual analogue scale scores
|
Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
|
|
Treatment Side-Effect Bother Assessed by FACT-GP5
Časové okno: Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
|
Defined as participants' responses to FACT-GP5 regarding how bothered they were by treatment side effects during the previous 7 days
|
Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
|
|
Symptomatic Adverse Events Assessed by PRO-CTCAE
Časové okno: Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
|
Defined as participant-reported frequency, severity, or interference of selected symptomatic adverse events using the PRO-CTCAE
|
Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months)
|
|
Participants With Treatment-Emergent Adverse Events
Časové okno: Assessed from the first dose of study treatment through 28 days after the last dose (up to 48 months)
|
Defined as the number and percentage of participants with adverse events that begin or worsen after the first dose of study treatment
|
Assessed from the first dose of study treatment through 28 days after the last dose (up to 48 months)
|
|
Change From Baseline in Electrocardiogram Parameters
Časové okno: Assessed at baseline and protocol-specified visits during treatment through the 28-day post-treatment follow-up visit (up to 48 months)
|
Defined as changes from baseline and clinically significant abnormalities in protocol-specified 12-lead electrocardiogram parameters
|
Assessed at baseline and protocol-specified visits during treatment through the 28-day post-treatment follow-up visit (up to 48 months)
|
|
Change From Baseline in Vital Signs
Časové okno: Assessed at baseline and protocol-specified visits during treatment through the 28-day post-treatment follow-up visit (up to 48 months)
|
Defined as changes from baseline and clinically significant abnormalities in protocol-specified vital-sign measurements
|
Assessed at baseline and protocol-specified visits during treatment through the 28-day post-treatment follow-up visit (up to 48 months)
|
|
Participants With Laboratory Abnormalities
Časové okno: Assessed at baseline and protocol-specified visits during treatment through the 28-day post-treatment follow-up visit (up to 48 months)
|
Defined as the number and percentage of participants with hematology, chemistry, or other protocol-specified laboratory abnormalities
|
Assessed at baseline and protocol-specified visits during treatment through the 28-day post-treatment follow-up visit (up to 48 months)
|
|
Plasma Concentrations of Inobrodib
Časové okno: Assessed at protocol-specified predose and postdose time points during treatment (up to 48 months)
|
Defined as the measured plasma concentrations of inobrodib and, where analyzed, its primary metabolite CCS1532
|
Assessed at protocol-specified predose and postdose time points during treatment (up to 48 months)
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Sponzor
Vyšetřovatelé
Vyšetřovatelé
- Ředitel studie: Study Director, CellCentric Ltd.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Odhadovaný)
Začátek studia
1. srpna 2026
Primární dokončení (Odhadovaný)
Primární dokončení
1. listopadu 2029
Dokončení studie (Odhadovaný)
Dokončení studie
1. listopadu 2031
Termíny zápisu do studia
První předloženo
První předloženo
13. srpna 2026
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
17. srpna 2026
První zveřejněno (Aktuální)
První zveřejněno
19. srpna 2026
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
19. srpna 2026
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
17. srpna 2026
Naposledy ověřeno
Naposledy ověřeno
1. srpna 2026
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
Další identifikační čísla studie
- CCS1477-05
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
NE
Popis plánu IPD
The final clinical study report will be provided to the Investigators.
The Sponsor will publicly disclose study results through posting on ClinicalTrials.gov
and any other applicable public registries in accordance with local regulations.
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Ano
Studuje produkt zařízení regulovaný americkým úřadem FDA
Ne
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .