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

Overview

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.

Interventions

• Drug Daratumumab Injection
  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)
• Drug Dexamethasone
  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)
• Drug Lenalidomide capsule
  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)

Primary outcome measures

• Compare Event-Free Survival (EFS) [Time frame: Approximately up to 57 (EFS) months after randomization of the first patient]
• Compare Progression Free Survival (PFS) [Time frame: Approximately up to 69 (PFS) months after randomization of the first patient]

Secondary outcome measures (12)

• 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]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Netherlands · 38 centers

• NL-Den Bosch-JBZ — 's-Hertogenbosch
• NL-Almere-FLEVOZIEKENHUIS — Almere Stad
• NL-Amersfoort-MEANDERMC — Amersfoort
• NL-Amsterdam- UMC — Amsterdam
• NL-Amsterdam-AmsterdamUMC — Amsterdam
• NL-Apeldoorn-GELREAPELDOORN — Apeldoorn
• NL-Arnhem-RIJNSTATE — Arnhem
• NL-Assen-WZA — Assen
• … and 30 more centers

Identifiers

NCT: NCT06187441 · HO174 · 2023-508586-33-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗