Multiple MyelomaPhase 3HOVON174MMNCT06187441
FeAsiBility of a Treatment Free Interval in Newly Diagnosed MM Patients Treated With Daratumumab-lenalidomide-dexamethasone (HOVON174MM)
A Phase 3 study testing Daratumumab Injection, Dexamethasone and Lenalidomide capsule in people with Multiple Myeloma, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 38 sites in Netherlands.
Trial summary
In the Netherlands, the standard treatment for multiple myeloma is a combination of different medicines named daratumumab-lenalidomide-dexamethasone, abbreviated as Dara-Rd. In many patients this treatment results in suppressing the disease for a long time. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Daratumumab Injection, Dexamethasone and Lenalidomide capsule
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 599 participants
- Where
- 38 sitesNetherlands
- Study dates
- 14 May 2024to Dec 2037
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient was diagnosed with MM, based on the IMWG criteria, and measurable disease at the time of diagnosis (appendix A).
- Age ≥ 18 years.
- Patient was treated with 12 cycles (13 cycles is accepted) of Dara-Rd and will continue treatment with Dara-Rd. Reduced dosing of lenalidomide, but not to less than 5 mg, and previous discontinuation or dose reduction of dexamethasone is allowed.
- Partial response or better after treatment with 12 cycles of Dara-Rd, without signs of biochemical progression.
- ANC ≥ 1.0x109/L and platelets ≥ 75x109/L.
- Patient is capable of giving informed consent.
- Written informed consent.
Who cannot join
- Patient with non-secretory MM at diagnosis of the disease, i.e., before the start of treatment with Dara-Rd.
- Patient in whom a plasmacytoma was the only measurable parameter at diagnosis of the disease, i.e., before the start of treatment with Dara-Rd.
- Patient in whom urine M-protein was the only measurable parameter at diagnosis of the disease, i.e., before the start of treatment with Dara-Rd.
- Patient in whom treatment with daratumumab, lenalidomide or both has been discontinued for whatever reason (patients may only have discontinued dexamethasone).
- Patient in whom continuation of treatment with Dara-Rd is deemed not feasible because of medical reasons.
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Trial locations and contacts
38 sites in 1 country. Contact the study team or a site near you to ask about taking part.
38 sites in 1 country
Netherlands38 sites, 38 recruiting
- Recruiting
NL-Den Bosch-JBZ
's-Hertogenbosch
- Recruiting
NL-Almere-FLEVOZIEKENHUIS
Almere Stad
- Recruiting
NL-Amersfoort-MEANDERMC
Amersfoort
- Recruiting
NL-Amsterdam- UMC
Amsterdam
- Recruiting
NL-Amsterdam-AmsterdamUMC
Amsterdam
- Recruiting
NL-Apeldoorn-GELREAPELDOORN
Apeldoorn
- Recruiting
NL-Arnhem-RIJNSTATE
Arnhem
- Recruiting
NL-Assen-WZA
Assen
- Recruiting
NL-Beverwijk-RKZ
Beverwijk
- Recruiting
NL-Delft-RDGG
Delft
- Recruiting
NL-Deventer-DZ
Deventer
- Recruiting
NL-Dordrecht-ASZ
Dordrecht
- Recruiting
Nij Smellinghe Ziekenhuis
Drachten
- Recruiting
NL-Ede-ZGV
Ede
- Recruiting
NL-Emmen-SCHEPER
Emmen
- Recruiting
NL-Enschede-MST
Enschede
- Recruiting
NL-Goes-ADRZ
Goes
- Recruiting
NL-Gorinchem-BEATRIX
Gorinchem
- Recruiting
NL-Groningen-MARTINI
Groningen
- Recruiting
NL-Hardenberg-SAXENBURGH
Hardenberg
- Recruiting
NL-Harderwijk-STJANSDALHARDERWIJK
Harderwijk
- Recruiting
NL-Helmond-ELKERLIEK
Helmond
- Recruiting
NL-Hilversum-TERGOOI
Hilversum
- Recruiting
NL-Hoofddorp-SPAARNEGASTHUIS
Hoofddorp
- Recruiting
NL-Hoorn-DIJKLANDERHOORN
Hoorn
- Recruiting
Alrijne Ziekenhuis Leiderdorp
Leiderdorp
- Recruiting
HMC Antoniushove
Leidschendam
- Recruiting
NL-Roosendaal-BRAVIS
Roosendaal
- Recruiting
NL-Rotterdam-IKAZIA
Rotterdam
- Recruiting
NL-Schiedam-FRANCISCUSVLIETLAND
Schiedam
- Recruiting
NL-Sittard-Geleen-ZUYDERLAND
Sittard
- Recruiting
NL-Sneek-ANTONIUSSNEEK
Sneek
- Recruiting
NL-Terneuzen-ZORGSAAM
Terneuzen
- Recruiting
NL-Tilburg-ETZ
Tilburg
- Recruiting
NL-Uden-BERNHOVEN
Uden
- Recruiting
NL-Venlo-VIECURI
Venlo
- Recruiting
NL-Zaandam-ZAANSMC
Zaandam
- Recruiting
NL-Zwolle-ISALA
Zwolle
About this study
Official title: FeAsiBility of a Treatment Free Interval in Newly Diagnosed mUltiple myeLOma Patients Treated With DaratumUmab-Lenalidomide-DexamethaSone- the FABULOUS Study. A Nationwide Open-label Randomized Phase III Clinical Trial Comparing Daratumumab-lenalidomide-dexamethasone Continuously Versus Including a Treatment Free Interval
In the Netherlands, the standard treatment for multiple myeloma is a combination of different medicines named daratumumab-lenalidomide-dexamethasone, abbreviated as Dara-Rd. In many patients this treatment results in suppressing the disease for a long time. The treatment is continued until it is not effective anymore and the disease progresses.
But until now it is unknown whether continuous therapy also leads to prolonging life. In addition, there are concerns about side effects, leading to a reduced quality of life, the development of severe toxicity that remains, which hampers subsequent therapy, and high costs due to prolonged treatment.
There are indications that temporarily stopping treatment is safe, leading to fewer side effects and allows recovering from toxicity or damage due to treatment. This may improve the quality of life.
- Conditions
- Multiple Myeloma
- Being tested
- Daratumumab Injection, Dexamethasone, Lenalidomide capsule
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Daratumumab InjectionDrug
Patients who have been treated with 12 cycles of Daratumumab-Lenalidomide-Dexamethasone (Dara-Rd) will be randomized between Arm A (continuous therapy) and Arm B (treatment free interval)
DexamethasoneDrug
Patients who have been treated with 12 cycles of Daratumumab-Lenalidomide-Dexamethasone (Dara-Rd) will be randomized between Arm A (continuous therapy) and Arm B (treatment free interval)
Lenalidomide capsuleDrug
Patients who have been treated with 12 cycles of Daratumumab-Lenalidomide-Dexamethasone (Dara-Rd) will be randomized between Arm A (continuous therapy) and Arm B (treatment free interval)
| Study group | Role | What they receive |
|---|---|---|
| Arm A | No intervention | A continuous therapy arm - continuation of therapy with Dara-Rd until PD |
| Arm B | Experimental | treatment free interval arm - discontinuation of therapy with Dara-Rd, which will be resumed at biochemical progression and given until PD Receives: Drug: Daratumumab Injection; Drug: Dexamethasone; Drug: Lenalidomide capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compare Event-Free Survival (EFS)
To compare Event-Free Survival (EFS) from the time of randomization, between arm A continuous therapy with Dara-Rd until PD versus arm B discontinuation of therapy with Dara-Rd, resuming therapy at the first signs of biochemical progression until PD
Measured: Approximately up to 57 (EFS) months after randomization of the first patient
Compare Progression Free Survival (PFS)
To compare Progression Free Survival (PFS) from the time of randomization, between arm A continuous therapy with Dara-Rd until PD versus arm B discontinuation of therapy with Dara-Rd, resuming therapy at the first signs of biochemical progression until PD
Measured: Approximately up to 69 (PFS) months after randomization of the first patient
Secondary outcomes (14)
Compare adverse event burden
To compare adverse event (AE) burden between arms
Measured: Approximately up to 69 months after randomization of the first patient
Compare patient-reported outcome measures (PROMs)
To compare PROMs between arms via validated questionnaires such as Impact of Cancer version 2 Cancer Worry scale
Measured: Approximately up to 69 months after randomization of the first patient
Compare cost-effectiveness between arms
To compare cost-effectiveness between arms
Measured: Approximately up to 69 months after randomization of the first patient
Determine the length of the treatment-free interval
To determine the length of the treatment-free interval (TFI) in arm B
Measured: Approximately up to 69 months after randomization of the first patient
Determine time to (maximal) response response
To determine time to (maximal) response after restart of Dara-Rd in arm B.
Measured: Approximately up to 69 months after randomization of the first patient
Compare time to next treatment
To compare time to next treatment (TTNT) between arms
Measured: Approximately up to 69 months after randomization of the first patient
Compare time from randomization to progression on second-line therapy
To compare time from randomization to progression on second-line therapy (PFS2) between arms.
Measured: Approximately up to 69 months after randomization of the first patient
Compare Overall Survival
To compare Overall Survival (OS) between arms.
Measured: Approximately up to 69 months after randomization of the last patient
Compare the discontinuation rate
To compare the discontinuation rate and the reasons for discontinuation between arms.
Measured: Approximately up to 69 months after randomization of the first patient
Evaluate cumulative doses
To evaluate cumulative dose of daratumumab, lenalidomide and dexamethasone in both arms.
Measured: Approximately up to 69 months after randomization of the first patient
Compare dose reductions
To compare dose reductions of daratumumab, lenalidomide and dexamethasone between arms.
Measured: Approximately up to 69 months after randomization of the first patient
Compare toxicity
To compare toxicity according to CTCAE v5 between arms
Measured: Approximately up to 69 months after randomization of the first patient
Compare Quality of Life
To compare Quality of Life between arms via validated questionnaires such as QLQ-C30, MY20, EQ-5D-5L
Measured: Approximately up to 69 months after randomization of the first patient
Compare relative dose intensity
To compare relative dose intensity (RDI) of daratumumab, lenalidomide and dexamethasone between arms.
Measured: Approximately up to 69 months after randomization of the first patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2024
- Study start14 May 2024
- Primary completionJan 2031 (estimated)
- Study completionDec 2037 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 599 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stichting Hemato-Oncologie voor Volwassenen Nederland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sonja Zweegman, Prof Dr MD, Principal investigator, Amsterdam UMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06187441
- Sponsor's protocol ID
- HO174
- Other IDs
- 2023-508586-33-00, 2023
- Acronym
- HOVON174MM
- Status last verified
- Aug 2024
- First submitted
- 1 Dec 2023
- Last updated
- 19 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FeAsiBility of a Treatment Free Interval in Newly Diagnosed mUltiple myeLOma Patients Treated With DaratumUmab-Lenalidomide-DexamethaSone- the FABULOUS Study. A Nationwide Open-label Randomized Phase III Clinical Trial Comparing Daratumumab-lenalidomide-dexamethasone Continuously Versus Including a Treatment Free Interval
- ClinicalTrials.gov ID
- NCT06187441
- Acronym / sponsor ID
- HOVON174MM / HO174
- Conditions
- Multiple Myeloma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 599 participants (estimated)
- Lead sponsor
- Stichting Hemato-Oncologie voor Volwassenen NederlandUniversity, hospital or other
- Study start
- 14 May 2024 (actual)
- Primary completion
- Jan 2031 (estimated)
- Study completion
- Dec 2037 (estimated)
- First posted
- 2 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the Netherlands, the standard treatment for multiple myeloma is a combination of different medicines named daratumumab-lenalidomide-dexamethasone, abbreviated as Dara-Rd. In many patients this treatment results in suppressing the disease for a long time. The treatment is continued until it is not effective anymore and the disease progresses.
But until now it is unknown whether continuous therapy also leads to prolonging life. In addition, there are concerns about side effects, leading to a reduced quality of life, the development of severe toxicity that remains, which hampers subsequent therapy, and high costs due to prolonged treatment.
There are indications that temporarily stopping treatment is safe, leading to fewer side effects and allows recovering from toxicity or damage due to treatment. This may improve the quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | No intervention | –A continuous therapy arm - continuation of therapy with Dara-Rd until PD |
| Arm B | Experimental | Drug: Daratumumab Injection, Drug: Dexamethasone, Drug: Lenalidomide capsuletreatment free interval arm - discontinuation of therapy with Dara-Rd, which will be resumed at biochemical progression and given until PD |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patient was diagnosed with MM, based on the IMWG criteria, and measurable disease at the time of diagnosis (appendix A).
- Age ≥ 18 years.
- Patient was treated with 12 cycles (13 cycles is accepted) of Dara-Rd and will continue treatment with Dara-Rd. Reduced dosing of lenalidomide, but not to less than 5 mg, and previous discontinuation or dose reduction of dexamethasone is allowed.
- Partial response or better after treatment with 12 cycles of Dara-Rd, without signs of biochemical progression.
- ANC ≥ 1.0x109/L and platelets ≥ 75x109/L.
Key exclusion criteria (6 listed)
- Patient with non-secretory MM at diagnosis of the disease, i.e., before the start of treatment with Dara-Rd.
- Patient in whom a plasmacytoma was the only measurable parameter at diagnosis of the disease, i.e., before the start of treatment with Dara-Rd.
- Patient in whom urine M-protein was the only measurable parameter at diagnosis of the disease, i.e., before the start of treatment with Dara-Rd.
- Patient in whom treatment with daratumumab, lenalidomide or both has been discontinued for whatever reason (patients may only have discontinued dexamethasone).
- Patient in whom continuation of treatment with Dara-Rd is deemed not feasible because of medical reasons.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Daratumumab InjectionPatients who have been treated with 12 cycles of Daratumumab-Lenalidomide-Dexamethasone (Dara-Rd) will be randomized between Arm A (continuous therapy) and Arm B (treatment free interval) | Drug | Arm B |
| DexamethasonePatients who have been treated with 12 cycles of Daratumumab-Lenalidomide-Dexamethasone (Dara-Rd) will be randomized between Arm A (continuous therapy) and Arm B (treatment free interval) | Drug | Arm B |
| Lenalidomide capsulePatients who have been treated with 12 cycles of Daratumumab-Lenalidomide-Dexamethasone (Dara-Rd) will be randomized between Arm A (continuous therapy) and Arm B (treatment free interval) | Drug | Arm B |
Primary outcome
Compare Event-Free Survival (EFS)
Time frame: Approximately up to 57 (EFS) months after randomization of the first patient
To compare Event-Free Survival (EFS) from the time of randomization, between arm A continuous therapy with Dara-Rd until PD versus arm B discontinuation of therapy with Dara-Rd, resuming therapy at the first signs of biochemical progression until PD
Compare Progression Free Survival (PFS)
Time frame: Approximately up to 69 (PFS) months after randomization of the first patient
To compare Progression Free Survival (PFS) from the time of randomization, between arm A continuous therapy with Dara-Rd until PD versus arm B discontinuation of therapy with Dara-Rd, resuming therapy at the first signs of biochemical progression until PD
14 secondary outcomes
Compare adverse event burden
Time frame: Approximately up to 69 months after randomization of the first patient
Compare patient-reported outcome measures (PROMs)
Time frame: Approximately up to 69 months after randomization of the first patient
Compare cost-effectiveness between arms
Time frame: Approximately up to 69 months after randomization of the first patient
Determine the length of the treatment-free interval
Time frame: Approximately up to 69 months after randomization of the first patient
Determine time to (maximal) response response
Time frame: Approximately up to 69 months after randomization of the first patient
Compare time to next treatment
Time frame: Approximately up to 69 months after randomization of the first patient
Compare time from randomization to progression on second-line therapy
Time frame: Approximately up to 69 months after randomization of the first patient
Compare Overall Survival
Time frame: Approximately up to 69 months after randomization of the last patient
Compare the discontinuation rate
Time frame: Approximately up to 69 months after randomization of the first patient
Evaluate cumulative doses
Time frame: Approximately up to 69 months after randomization of the first patient
Compare dose reductions
Time frame: Approximately up to 69 months after randomization of the first patient
Compare toxicity
Time frame: Approximately up to 69 months after randomization of the first patient
Compare Quality of Life
Time frame: Approximately up to 69 months after randomization of the first patient
Compare relative dose intensity
Time frame: Approximately up to 69 months after randomization of the first patient
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2024.
- HOVON websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sonja Zweegman, Prof Dr MD principal investigator
Amsterdam UMC
38 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Daratumumab Injection, Dexamethasone and Lenalidomide capsule in people with Multiple Myeloma, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 38 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sonja Zweegman, Prof Dr MD (0031 20 4442604 ext. 61467, s.zweegman@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Compare Event-Free Survival (EFS) (time frame: Approximately up to 57 (EFS) months after randomization of the first patient). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2024.