Clinical trial NCT06187441: FeAsiBility of a Treatment Free Interval in Newly Diagnosed MM Patients Treated With Daratumumab-lenalidomide-dexamethasone (HOVON174MM)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Multiple Myeloma
Lead sponsor: Stichting Hemato-Oncologie voor Volwassenen Nederland
Sponsor class: OTHER
First posted: 2024-01-02
Enrollment: 599
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Compare Event-Free Survival (EFS)
timeFrame: Approximately up to 57 (EFS) months after randomization of the first patient
measure: Compare Progression Free Survival (PFS)
timeFrame: Approximately up to 69 (PFS) months after randomization of the first patient
Secondary outcomes:
measure: Compare adverse event burden
timeFrame: Approximately up to 69 months after randomization of the first patient
measure: Compare patient-reported outcome measures (PROMs)
timeFrame: Approximately up to 69 months after randomization of the first patient
measure: Compare cost-effectiveness between arms
timeFrame: Approximately up to 69 months after randomization of the first patient
measure: Determine the length of the treatment-free interval
timeFrame: Approximately up to 69 months after randomization of the first patient
measure: Determine time to (maximal) response response
timeFrame: Approximately up to 69 months after randomization of the first patient
measure: Compare time to next treatment
timeFrame: Approximately up to 69 months after randomization of the first patient
measure: Compare time from randomization to progression on second-line therapy
timeFrame: Approximately up to 69 months after randomization of the first patient
measure: Compare Overall Survival
timeFrame: Approximately up to 69 months after randomization of the last patient
measure: Compare the discontinuation rate
timeFrame: Approximately up to 69 months after randomization of the first patient
measure: Evaluate cumulative doses
timeFrame: Approximately up to 69 months after randomization of the first patient
measure: Compare dose reductions
timeFrame: Approximately up to 69 months after randomization of the first patient
measure: Compare toxicity
timeFrame: Approximately up to 69 months after randomization of the first patient
measure: Compare Quality of Life
timeFrame: Approximately up to 69 months after randomization of the first patient
measure: Compare relative dose intensity
timeFrame: Approximately up to 69 months after randomization of the first patient
Other outcomes:
Locations:
city: Almere
country: Netherlands
facility: NL-Almere-FLEVOZIEKENHUIS
city: Amersfoort
country: Netherlands
facility: NL-Amersfoort-MEANDERMC
city: Amsterdam
country: Netherlands
facility: NL-Amsterdam- UMC
city: Amsterdam
country: Netherlands
facility: NL-Amsterdam-AmsterdamUMC
city: Apeldoorn
country: Netherlands
facility: NL-Apeldoorn-GELREAPELDOORN
city: Arnhem
country: Netherlands
facility: NL-Arnhem-RIJNSTATE
city: Assen
country: Netherlands
facility: NL-Assen-WZA
city: Beverwijk
country: Netherlands
facility: NL-Beverwijk-RKZ
city: Delft
country: Netherlands
facility: NL-Delft-RDGG
city: Den Bosch
country: Netherlands
facility: NL-Den Bosch-JBZ
city: Deventer
country: Netherlands
facility: NL-Deventer-DZ
city: Dordrecht
country: Netherlands
facility: NL-Dordrecht-ASZ
city: Drachten
country: Netherlands
facility: Nij Smellinghe Ziekenhuis
city: Ede
country: Netherlands
facility: NL-Ede-ZGV
city: Emmen
country: Netherlands
facility: NL-Emmen-SCHEPER
city: Enschede
country: Netherlands
facility: NL-Enschede-MST
city: Goes
country: Netherlands
facility: NL-Goes-ADRZ
city: Gorinchem
country: Netherlands
facility: NL-Gorinchem-BEATRIX
city: Groningen
country: Netherlands
facility: NL-Groningen-MARTINI
city: Hardenberg
country: Netherlands
facility: NL-Hardenberg-SAXENBURGH
city: Harderwijk
country: Netherlands
facility: NL-Harderwijk-STJANSDALHARDERWIJK
city: Helmond
country: Netherlands
facility: NL-Helmond-ELKERLIEK
city: Hilversum
country: Netherlands
facility: NL-Hilversum-TERGOOI
city: Hoofddorp
country: Netherlands
facility: NL-Hoofddorp-SPAARNEGASTHUIS
city: Hoorn
country: Netherlands
facility: NL-Hoorn-DIJKLANDERHOORN
city: Leiderdorp
country: Netherlands
facility: Alrijne Ziekenhuis Leiderdorp
city: Leidschendam
country: Netherlands
facility: HMC Antoniushove
city: Roosendaal
country: Netherlands
facility: NL-Roosendaal-BRAVIS
city: Rotterdam
country: Netherlands
facility: NL-Rotterdam-IKAZIA
city: Schiedam
country: Netherlands
facility: NL-Schiedam-FRANCISCUSVLIETLAND
city: Sittard
country: Netherlands
facility: NL-Sittard-Geleen-ZUYDERLAND
city: Sneek
country: Netherlands
facility: NL-Sneek-ANTONIUSSNEEK
city: Terneuzen
country: Netherlands
facility: NL-Terneuzen-ZORGSAAM
city: Tilburg
country: Netherlands
facility: NL-Tilburg-ETZ
city: Uden
country: Netherlands
facility: NL-Uden-BERNHOVEN
city: Venlo
country: Netherlands
facility: NL-Venlo-VIECURI
city: Zaandam
country: Netherlands
facility: NL-Zaandam-ZAANSMC
city: Zwolle
country: Netherlands
facility: NL-Zwolle-ISALA
Study officials:
affiliation: Amsterdam UMC
name: Sonja Zweegman, Prof Dr MD
role: PRINCIPAL_INVESTIGATOR
References: