Clinical trial • Phase III • Oncology
DEXAMETHASONE for Multiple myeloma
Phase III trial of DEXAMETHASONE for Multiple myeloma.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Multiple myeloma
- Trial Stage
- Phase III
- Drug Modality
- Monoclonal antibody|Small molecule
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 15-01-2024
- First CTIS Authorization Date
- 11-03-2024
Trial design
Randomised, arm a: continuous therapy with dara-rd until progressive disease. arm b: discontinuation of therapy with dara-rd, resuming therapy at biochemical progression until progressive disease. doses and schedules are not specified in the ctis record.-controlled Phase III trial across 64 sites in Netherlands.
- Randomised
- Yes
- Comparator
- Arm A: continuous therapy with Dara-Rd until Progressive Disease. Arm B: discontinuation of therapy with Dara-Rd, resuming therapy at biochemical progression until Progressive Disease. Doses and schedules are not specified in the CTIS record.
- Target Sample Size
- 599
Eligibility
Recruits 599 No vulnerable populations selected (isVulnerablePopulationSelected: false). Participants must be age ≥ 18 years and must be capable of giving informed consent; written informed consent is required from the participant..
- Vulnerable Population
- No vulnerable populations selected (isVulnerablePopulationSelected: false). Participants must be age ≥ 18 years and must be capable of giving informed consent; written informed consent is required from the participant.
Inclusion criteria
- {"criterion_text":"- Patient was diagnosed with MM, based on the IMWG criteria, and measurable disease at the time of diagnosis (appendix A of the protocol)\n- Age ≥ 18 years\n- 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.\n- 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\n- ANC ≥ 1.0x109/L (G-CSF may be administered to meet this requirement) and platelets ≥ 75x109/L\n- Patient is capable of giving informed consent\n- Written informed consent"}
Exclusion criteria
- {"criterion_text":"- Patient with non-secretory MM at diagnosis of the disease, i.e., before the start of treatment with Dara-Rd\n- 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\n- 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\n- Patient in whom treatment with daratumumab, lenalidomide or both has been discontinued for whatever reason (patients may only have discontinued dexamethasone)\n- Patient in whom continuation of treatment with Dara-Rd is deemed not feasible because of medical reasons\n- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule\n- Patients with plasma cell leukemia.\n- 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.\n- 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 endpoints
- {"endpoint_text":"- 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)","definition_or_measurement_approach":"Events are 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. See protocol section 10.4 for definitions of PD and biochemical progression."}
- {"endpoint_text":"- 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","definition_or_measurement_approach":"Events are defined as PD (according to the definition in protocol section 10.4) or death."}
Secondary endpoints
- {"endpoint_text":"- Toxicity, according to CTCAE v5","definition_or_measurement_approach":"Toxicity will be graded according to CTCAE version 5."}
- {"endpoint_text":"- Adverse event (AE) burden","definition_or_measurement_approach":""}
- {"endpoint_text":"- Quality of Life and PROMs","definition_or_measurement_approach":""}
- {"endpoint_text":"- Cost-effectiveness analysis","definition_or_measurement_approach":""}
- {"endpoint_text":"- Treatment-free interval (TFI) in arm B","definition_or_measurement_approach":""}
- {"endpoint_text":"- Time to response and to maximal response after restart of Dara-Rd in arm B","definition_or_measurement_approach":""}
- {"endpoint_text":"- Time to next treatment (TTNT)","definition_or_measurement_approach":""}
- {"endpoint_text":"- PFS2 from the time of randomization to 2nd PD or death, whichever comes first","definition_or_measurement_approach":""}
- {"endpoint_text":"- OS from time of randomization to death from any cause; patients still alive at the date of last contact will be censored","definition_or_measurement_approach":"Overall survival measured from randomization to death from any cause; censoring at date of last contact for those alive."}
- {"endpoint_text":"- Discontinuation rate and the reasons for discontinuation","definition_or_measurement_approach":""}
- {"endpoint_text":"- Cumulative dose and relative dose intensity (RDI) of daratumumab, lenalidomide and dexamethasone","definition_or_measurement_approach":""}
- {"endpoint_text":"- Dose reductions of daratumumab, lenalidomide and dexamethasone","definition_or_measurement_approach":""}
Recruitment
- Planned Sample Size
- 599
- Recruitment Window Months
- 76
- Consent Approach
- Written informed consent is required. Inclusion criteria state that the patient 'is capable of giving informed consent' and 'Written informed consent' is required. No paediatric assent procedures are indicated (participants must be ≥ 18 years). ICF documents are listed in the CTIS documents (e.g. 'L1 HO174 SIS and ICF').
Geography
- Total Number Of Sites
- 64
- Total Number Of Participants
- 599
Netherlands
- Earliest CTIS Part Ii Submission Date
- 22-02-2024
- Latest Decision Or Authorization Date
- 10-04-2026
- Processing Time Days
- 778
- Number Of Sites
- 64
- Number Of Participants
- 599
Sites
- Site Name
- University Hospital Maastricht
- Department Name
- Hematology
- Contact Person Name
- j. van Elssen
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Rijnstate Ziekenhuis Stichting
- Department Name
- Interne geneeskunde
- Contact Person Name
- E. van der Spek
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Amsterdam UMC
- Department Name
- Hematologie
- Contact Person Name
- S. Zweegman
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- IJsselland Ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- R.F.J. Schop
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Canisius Wilhelmina Hospital
- Department Name
- Interne geneeskunde
- Contact Person Name
- M. Oosterveld
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Sint Franciscus Vlietland Groep Stichting
- Department Name
- Hematology
- Contact Person Name
- H. Boiten
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Noordwest Ziekenhuisgroep Stichting
- Department Name
- Hematolgy
- Contact Person Name
- M Westerman
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Antonius ziekenhuis Sneek
- Department Name
- Interne geneeskunde
- Contact Person Name
- L.M. van der Burg
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Zuyderland Medisch Centrum Stichting
- Department Name
- Interne geneeskunde
- Contact Person Name
- R.J.W. van Kampen
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Stichting Martini Ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- J. Schreurs
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Bravis Ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- N.C.H.P. de Graauw
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Meander Medisch Centrum
- Department Name
- Interne geneeskunde
- Contact Person Name
- J.C. Regelink
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Universitair Medisch Centrum Groningen
- Department Name
- Hematology
- Contact Person Name
- W.W.H. Roeloffzen
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Medisch Spectrum Twente
- Department Name
- Hematology
- Contact Person Name
- C.R. van Rooijen
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Beatrix Ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- M. Last-Koopmans
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Ziekenhuis Nij Smellinghe
- Department Name
- Interne geneeskunde
- Contact Person Name
- L.F. Schipper
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Wilhelmina Ziekenhuis Assen
- Department Name
- Hematology
- Contact Person Name
- T. Wustman
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Reinier de Graaf Groep
- Department Name
- Interne geneeskunde
- Contact Person Name
- S.U. Soechit
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Maasstad Ziekenhuis Stichting
- Department Name
- Hematology
- Contact Person Name
- Y. Sandberg
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Admiraal de Ruijter ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- S. Kuipers
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Elkerliek Ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- M. Zanders
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Medical Center Haaglanden
- Department Name
- Interne geneeskunde
- Contact Person Name
- L. te Boome
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Rode Kruis Ziekenhuis B.V.
- Department Name
- Hematology
- Contact Person Name
- F.S. Kleijwegt
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- ZorgSaam Ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- N.C. van Yperen
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Diakonessenhuis Stichting
- Department Name
- Interne geneeskunde
- Contact Person Name
- N. Thielen
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Ziekenhuisgroep Twente Stichting
- Department Name
- Interne geneeskunde
- Contact Person Name
- B. Schot
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Zaans Medisch Centrum Stichting
- Department Name
- interne geneeskunde
- Contact Person Name
- K.G. van der Hem
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Isala Klinieken Stichting
- Department Name
- Interne geneeskunde
- Contact Person Name
- P. Geerts
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Maxima Medisch Centrum
- Department Name
- Hematology
- Contact Person Name
- L.W. Tick
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Gelre Hospitals
- Department Name
- Interne geneeskunde
- Contact Person Name
- C.G. Schaar
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Tergooiziekenhuizen
- Department Name
- Interne geneeskunde
- Contact Person Name
- E. Weerd de - de Jong
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- St. Jans Gasthuis
- Department Name
- Hematology
- Contact Person Name
- A. Graaf, de-van den Brok
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Slingeland Ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- J. van Heek
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Spaarne Gasthuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- A. Griffioen- Keijzer
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Ommelander Ziekenhuis Groningen B.V.
- Department Name
- Interne geneeskunde
- Contact Person Name
- S. Meijering
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Flevoziekenhuis Stichting
- Department Name
- Interne geneeskunde
- Contact Person Name
- K. de Heer
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Saxenburgh Medisch Centrum
- Department Name
- Interne geneeskunde
- Contact Person Name
- Y. Tromp
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Ziekenhuis Gelderse Vallei Stichting
- Department Name
- Interne geneeskunde
- Contact Person Name
- G.A. Velders
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- St. Anna Ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- D. Willemsen
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Frisius MC
- Department Name
- Hematology
- Contact Person Name
- B. van Rees
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Catharina Ziekenhuis Stichting
- Department Name
- Interne geneeskunde
- Contact Person Name
- M. Nijziel
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Treant Ziekenhuiszorg Stichting
- Department Name
- Interne geneeskunde
- Contact Person Name
- F. Huisman
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Stichting OLVG
- Department Name
- interne geneeskunde
- Contact Person Name
- A.M. Gerrits
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Het Van Weel-Bethesda Ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- H.S. Noordzij-Nooteboom
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Haga Hospital
- Department Name
- Hematology
- Contact Person Name
- P. Ypma
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Ziekenhuis St Jansdal
- Department Name
- Interne geneeskunde
- Contact Person Name
- A.C. Dijk
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Ikazia Ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- M. Eefting
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Laurentius Ziekenhuis Roermond
- Department Name
- Interne geneeskunde
- Contact Person Name
- M.H.W. van de Poel
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Dijklander Ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- C.P.W. Klerk
- Site Name
- Maasziekenhuis Pantein B.V.
- Department Name
- Interne geneeskunde
- Contact Person Name
- B. van der Zouwen
- Site Name
- Deventer Ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- A. Breedijk
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Groene Hart Ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- T.H. Levenga
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Ziekenhuis Amstelland
- Department Name
- Interne geneeskunde
- Contact Person Name
- L.H. Schilder
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Ziekenhuis Rivierenland
- Department Name
- Interne geneeskunde
- Contact Person Name
- A. Kleinjan
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Stichting Viecuri Medisch Centrum voor Noord-Limburg
- Department Name
- Interne geneeskunde
- Contact Person Name
- A. Koster
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Alrijne Zorggroep Stichting
- Department Name
- Interne geneeskunde
- Contact Person Name
- L. Hardi
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Jeroen Bosch Ziekenhuis
- Department Name
- Hematology
- Contact Person Name
- L. Franssen
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Bernhoven B.V.
- Department Name
- Interne geneeskunde
- Contact Person Name
- I. Ludwig
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Amphia Hospital
- Department Name
- Interne geneeskunde
- Contact Person Name
- M. van der Klift
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- St. Elisabeth Hospital Tilburg
- Department Name
- Hematology
- Contact Person Name
- J. Oudhoff
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Sint Antonius Ziekenhuis Stichting
- Department Name
- Hematology
- Contact Person Name
- I.S. Nijhof
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Frisius MC
- Department Name
- Hematology
- Contact Person Name
- E.G.M. de Waal
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Albert Schweitzer Ziekenhuis
- Department Name
- Interne geneeskunde
- Contact Person Name
- M.D. Levin
- Contact Person Email
- hovon@erasmusmc.nl
- Site Name
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Department Name
- Hematology
- Contact Person Name
- C.A.M. Stege
- Contact Person Email
- hovon@erasmusmc.nl
Sponsor
Primary sponsor
- Full Name
- Stichting Hemato-Oncologie voor Volwassenen Nederland (Hovon)
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- Netherlands
Third parties
- {"country":"Netherlands","full_name":"IMTA Erasmus University","duties_or_roles":"economic analysis","organisation_type":"Educational Institution"}
- {"country":"Netherlands","full_name":"Amsterdam UMC","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Netherlands","full_name":"IKNL","duties_or_roles":"local data collection and quality of life","organisation_type":"Laboratory/Research/Testing facility"}
Investigational products
- Investigational Product Name
- DEXAMETHASONE
- Active Substance
- DEXAMETHASONE
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- ORAL USE
- Maximum Dose
- 40 mg
- Investigational Product Name
- DARATUMUMAB
- Active Substance
- DARATUMUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- SUBCUTANEOUS INJECTION
- Route
- SUBCUTANEOUS INJECTION
- Orphan Designation
- Yes
- Maximum Dose
- 1800 mg
- Investigational Product Name
- LENALIDOMIDE
- Active Substance
- LENALIDOMIDE
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Maximum Dose
- 25 mg
- Combination Treatment
- Yes
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