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

December 14, 2023 updated by: Stichting Hemato-Oncologie voor Volwassenen Nederland

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

599

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Arm A
A continuous therapy arm - continuation of therapy with Dara-Rd until PD
Experimental: Arm B
treatment free interval arm - discontinuation of therapy with Dara-Rd, which will be resumed at biochemical progression and given until PD
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compare adverse event burden
Time Frame: Approximately up to 69 months after randomization of the first patient
To compare adverse event (AE) burden between arms
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
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
Compare cost-effectiveness between arms
Time Frame: Approximately up to 69 months after randomization of the first patient
To compare cost-effectiveness between arms
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
To determine the length of the treatment-free interval (TFI) in arm B
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
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
Compare time to next treatment
Time Frame: Approximately up to 69 months after randomization of the first patient
To compare time to next treatment (TTNT) between arms
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
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
Compare Overall Survival
Time Frame: Approximately up to 69 months after randomization of the last patient
To compare Overall Survival (OS) between arms.
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
To compare the discontinuation rate and the reasons for discontinuation between arms.
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
To evaluate cumulative dose of daratumumab, lenalidomide and dexamethasone in both arms.
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
To compare dose reductions of daratumumab, lenalidomide and dexamethasone between arms.
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
To compare toxicity according to CTCAE v5 between arms
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
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
Compare relative dose intensity
Time Frame: Approximately up to 69 months after randomization of the first patient
To compare relative dose intensity (RDI) of daratumumab, lenalidomide and dexamethasone between arms.
Approximately up to 69 months after randomization of the first patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stichting Hemato-Oncologie voor Volwassenen Nederland

Investigators

  • Principal Investigator: Sonja Zweegman, Prof Dr MD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2024

Primary Completion (Estimated)

January 1, 2031

Study Completion (Estimated)

December 1, 2037

Study Registration Dates

First Submitted

December 1, 2023

First Submitted That Met QC Criteria

December 14, 2023

First Posted (Estimated)

January 1, 2024

Study Record Updates

Last Update Posted (Estimated)

January 1, 2024

Last Update Submitted That Met QC Criteria

December 14, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HO174
  • 2023-508586-33-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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