Multiple Myeloma
Conditions
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.
Interventions
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)
DRUGDexamethasone
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)
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)
Sponsors
Stichting Hemato-Oncologie voor Volwassenen Nederland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compare Event-Free Survival (EFS) | 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) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare patient-reported outcome measures (PROMs) | Approximately up to 69 months after randomization of the first patient | To compare PROMs between arms via validated questionnaires such as Impact of Cancer version 2 Cancer Worry scale |
| Compare cost-effectiveness between arms | Approximately up to 69 months after randomization of the first patient | To compare cost-effectiveness between arms |
| Determine time to (maximal) response response | Approximately up to 69 months after randomization of the first patient | To determine time to (maximal) response after restart of Dara-Rd in arm B. |
| Compare time to next treatment | Approximately up to 69 months after randomization of the first patient | To compare time to next treatment (TTNT) between arms |
| Compare time from randomization to progression on second-line therapy | Approximately up to 69 months after randomization of the first patient | To compare time from randomization to progression on second-line therapy (PFS2) between arms. |
| Compare Overall Survival | Approximately up to 69 months after randomization of the last patient | To compare Overall Survival (OS) between arms. |
| Determine the length of the treatment-free interval | Approximately up to 69 months after randomization of the first patient | To determine the length of the treatment-free interval (TFI) in arm B |
| Evaluate cumulative doses | Approximately up to 69 months after randomization of the first patient | To evaluate cumulative dose of daratumumab, lenalidomide and dexamethasone in both arms. |
| Compare dose reductions | Approximately up to 69 months after randomization of the first patient | To compare dose reductions of daratumumab, lenalidomide and dexamethasone between arms. |
| Compare toxicity | Approximately up to 69 months after randomization of the first patient | To compare toxicity according to CTCAE v5 between arms |
| Compare Quality of Life | Approximately up to 69 months after randomization of the first patient | To compare Quality of Life between arms via validated questionnaires such as QLQ-C30, MY20, EQ-5D-5L |
| Compare relative dose intensity | Approximately up to 69 months after randomization of the first patient | To compare relative dose intensity (RDI) of daratumumab, lenalidomide and dexamethasone between arms. |
| Compare the discontinuation rate | Approximately up to 69 months after randomization of the first patient | To compare the discontinuation rate and the reasons for discontinuation between arms. |
| Compare adverse event burden | Approximately up to 69 months after randomization of the first patient | To compare adverse event (AE) burden between arms |
Countries
Netherlands
Contacts
Primary ContactSonja Zweegman, Prof Dr MD
Backup ContactMaarten Seefat, MD
Outcome results
None listed