FeAsiBility of a Treatment Free Interval in Newly Diagnosed MM Patients Treated With Daratumumab-lenalidomide-dexamethasone (HOVON174MM)

Multiple Myeloma Clinical Trial

— 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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06187441
• Other study ID #: HO174
• Secondary ID: 2023-508586-33-0
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 2024
• Est. completion date: December 2037

Study information

• Verified date: December 2023
• Source: Stichting Hemato-Oncologie voor Volwassenen Nederland
• Contact: Sonja Zweegman, Prof Dr MD
• Phone: 0031 20 4442604
• Email: s.zweegman[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 599
• Est. completion date: December 2037
• Est. primary completion date: January 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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)
• 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)
• 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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Stichting Hemato-Oncologie voor Volwassenen Nederland

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Approximately up to 57 (EFS) months after randomization of the first patient
Primary	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	Approximately up to 69 (PFS) months after randomization of the first patient
Secondary	Compare adverse event burden	To compare adverse event (AE) burden between arms	Approximately up to 69 months after randomization of the first patient
Secondary	Compare patient-reported outcome measures (PROMs)	To compare PROMs between arms via validated questionnaires such as Impact of Cancer version 2 Cancer Worry scale	Approximately up to 69 months after randomization of the first patient
Secondary	Compare cost-effectiveness between arms	To compare cost-effectiveness between arms	Approximately up to 69 months after randomization of the first patient
Secondary	Determine the length of the treatment-free interval	To determine the length of the treatment-free interval (TFI) in arm B	Approximately up to 69 months after randomization of the first patient
Secondary	Determine time to (maximal) response response	To determine time to (maximal) response after restart of Dara-Rd in arm B.	Approximately up to 69 months after randomization of the first patient
Secondary	Compare time to next treatment	To compare time to next treatment (TTNT) between arms	Approximately up to 69 months after randomization of the first patient
Secondary	Compare time from randomization to progression on second-line therapy	To compare time from randomization to progression on second-line therapy (PFS2) between arms.	Approximately up to 69 months after randomization of the first patient
Secondary	Compare Overall Survival	To compare Overall Survival (OS) between arms.	Approximately up to 69 months after randomization of the last patient
Secondary	Compare the discontinuation rate	To compare the discontinuation rate and the reasons for discontinuation between arms.	Approximately up to 69 months after randomization of the first patient
Secondary	Evaluate cumulative doses	To evaluate cumulative dose of daratumumab, lenalidomide and dexamethasone in both arms.	Approximately up to 69 months after randomization of the first patient
Secondary	Compare dose reductions	To compare dose reductions of daratumumab, lenalidomide and dexamethasone between arms.	Approximately up to 69 months after randomization of the first patient
Secondary	Compare toxicity	To compare toxicity according to CTCAE v5 between arms	Approximately up to 69 months after randomization of the first patient
Secondary	Compare Quality of Life	To compare Quality of Life between arms via validated questionnaires such as QLQ-C30, MY20, EQ-5D-5L	Approximately up to 69 months after randomization of the first patient
Secondary	Compare relative dose intensity	To compare relative dose intensity (RDI) of daratumumab, lenalidomide and dexamethasone between arms.	Approximately up to 69 months after randomization of the first patient

External Links

•   HOVON website