FeAsiBility of a treatment free interval in newly diagnosed mUltiple myeLOma patients treated with DaratumUmab-Lenalidomide-DexamethaSone – the FABULOUS study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Hemato-Oncologie voor Volwassenen Nederland (Hovon)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 May 2024 → ongoing

Decision date (initial)

2024-03-11

Transition trial

No

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

ZonMw · Treatmeds

External identifiers

EU CT number

2023-508586-33-00

ClinicalTrials.gov

NCT06187441

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Therapy, Pharmacoeconomic

To compare Event-Free Survival (EFS) and Progression Free Survival (PFS) from the time of randomization, between arm A continuous therapy with Dara-Rd until Progressive Disease versus arm B discontinuation of therapy with Dara-Rd, resuming therapy at biochemical progression until Progressive Disease.

Secondary objectives 11

1. To compare toxicity and adverse event (AE) burden between arms.
2. To compare Quality of Life (QoL) and additional PROMs between arms.
3. To compare costs and effects between arms and calculate cost-effectiveness.
4. To determine the length of the treatment-free interval (TFI) in arm B.
5. To determine time to response and to maximal response after restart of Dara-Rd in arm B.
6. To compare time to next treatment (TTNT) between arms
7. To compare PFS2 between arms.
8. To compare OS between arms.
9. To compare the discontinuation rate and the reasons for discontinuation between arms.
10. To evaluate cumulative dose and relative dose intensity (RDI) of daratumumab, lenalidomide and dexamethasone in both arms.
11. To compare dose reductions of daratumumab, lenalidomide and dexamethasone between arms.

Conditions and MedDRA coding

multiple myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patient was diagnosed with MM, based on the IMWG criteria, and measurable disease at the time of diagnosis (appendix A of the protocol)
2. Age ≥ 18 years
3. Patient was treated with 12 cycles (13 cycles is accepted) of Dara-Rd as 1st line treatment and is eligible to continue treatment with Dara-Rd. Reduced dosing of lenalidomide, but not to less than 5 mg/day*, and previous discontinuation or dose reduction of dexamethasone is allowed.Four or less cycles of an alternative treatment to Dara-Rd, immediately followed by Dara-Rd as 1st line treatment are allowed, provided that 1) a minimum of 12 and a maximum of 13 cycles of daratumumab-containing treatment cycles have been given before start HOVON174 protocol treatment and 2) there is confirmation from the medical monitor.
4. PR or better after treatment with 12 or 13 cycles of Dara-Rd (or Dara-containing regimen, see for explanation above), without signs of biochemical progression
5. ANC ≥ 1.0x109/L (G-CSF may be administered to meet this requirement) and platelets ≥ 75x109/L
6. Patient is capable of giving informed consent
7. Written informed consent

Exclusion criteria 9

1. Patient with non-secretory MM at diagnosis of the disease, i.e., before the start of treatment with Dara-Rd
2. 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
3. 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
4. Patient in whom treatment with daratumumab, lenalidomide or both has been discontinued for whatever reason (patients may only have discontinued dexamethasone)
5. Patient in whom continuation of treatment with Dara-Rd is deemed not feasible because of medical reasons
6. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
7. Patients with plasma cell leukemia.
8. Any history of malignancy other than MM which is considered at high risk of recurrence requiring treatment that affects bone marrow capacity or a malignancy that has been treated with chemotherapy currently affecting bone marrow capacity.
9. No active treatment with daratumumab or lenalidomide. Discontinuation of daratumumab or lenalidomide during previous cycles is permitted, but treatment should successfully be resumed at time of randomization Patient in whom treatment with daratumumab, lenalidomide or both has been discontinued for whatever reason (patients may only have discontinued dexamethasone).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Event free survival (EFS) from the time of randomization, with events being defined as: PD, death, going off protocol treatment due to toxicity, biochemical progression within 4 months after discontinuation of therapy in arm B or less than minimal response after 4 cycles of therapy after the restart of Dara-Rd in arm B, whichever comes first (see protocol section 10.4 for definitions of PD and biochemical progression)
2. Progression free survival (PFS) from the time of randomization, with events being defined as PD (according to definition in section 10.4) or death, whichever comes first

Secondary endpoints 12

1. Toxicity, according to CTCAE v5
2. Adverse event (AE) burden
3. Quality of Life and PROMs
4. Cost-effectiveness analysis
5. Treatment-free interval (TFI) in arm B
6. Time to response and to maximal response after restart of Dara-Rd in arm B
7. Time to next treatment (TTNT)
8. PFS2 from the time of randomization to 2nd PD or death, whichever comes first
9. OS from time of randomization to death from any cause; patients still alive at the date of last contact will be censored
10. Discontinuation rate and the reasons for discontinuation
11. Cumulative dose and relative dose intensity (RDI) of daratumumab, lenalidomide and dexamethasone
12. Dose reductions of daratumumab, lenalidomide and dexamethasone

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Hemato-Oncologie voor Volwassenen Nederland (Hovon)

Sponsor organisation

Stichting Hemato-Oncologie voor Volwassenen Nederland (Hovon)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Stichting Hemato-Oncologie voor Volwassenen Nederland (Hovon)

Contact name

Prof. Dr. S. Zweegman

Public contact point

Organisation

Stichting Hemato-Oncologie voor Volwassenen Nederland (Hovon)

Contact name

HOVON

Third parties 3

Locations

1 EU/EEA country · 64 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications