Clinical trial NCT01685814: Lenalidomide, Adriamycin, Dexamethasone (RAD) Versus Lenalidomide, Bortezomib, Dexamethasone (VRD) for Induction in Newly Diagnosed Multiple Myeloma Followed by Response-adapted Consolidation and Lenalidomide Maintenance
Official title: Lenalidomide, Adriamycin, Dexamethasone (RAD) Versus Lenalidomide, Bortezomib, Dexamethasone (VRD) for Induction in Newly Diagnosed Multiple Myeloma Followed by Response-adapted Consolidation and Lenalidomide Maintenance - A Randomized Multicenter Phase III Trial by Deutsche Studiengruppe Multiples Myelom (DSMM XIV
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Previously Untreated Symptomatic Multiple Myeloma
Keywords: multiple myeloma
autologous stem cell transplant
allogeneic stem cell transplant
lenalidomide
bortezomib
Lead sponsor: Wuerzburg University Hospital
Sponsor class: OTHER
Collaborators: name: ClinAssess GmbH
name: Celgene Corporation
First posted: 2012-09-14
Enrollment: 406
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators propose this study utilizing Lenalidomide, Adriamycin, Dexamethasone (RAD) as comparator arm for Lenalidomide, Bortezomib, Dexamethasone (VRD) with the latter being considered a novel "standard" as an induction protocol, since response in general occurs early after starting treatment we decided to choose three cycles of either induction regimen.

Together with the "novel compounds", tandem high-dose melphalan is still the standard of care; it seems desirable to re-address the question of the number of transplant (single vs. double high-dose melphalan) procedures required in the context of triplet-induction protocols utilizing at least one of the novel compounds.

Thus, the question to be asked in the current protocol is whether immediate lenalidomide maintenance (i.e. following one cycle of high-dose therapy) as an investigational agent will result in identical progression free survival (PFS) when compared to tandem high-dose melphalan with deferred maintenance therapy.

Despite induction with novel compounds, approximately 25 - 40% of patients will be in less than very good partial response. Very recently, achievement of less than VGPR was confirmed to negatively impact on both PFS as well as overall survival (OS). Therefore, allogeneic stem cell transplantation is considered the standard of care in patients with suboptimal response to a first autograft.

In the current protocol, the standard for favourable responders (tandem-autologous transplant) is combined with 3 years of lenalidomide maintenance. This approach will be investigated for patients with less than VGPR following a first autotransplant and compared to the current standard of intensification in poor responders (allogeneic transplantation).


Eligibility criteria: Inclusion Criteria:

* Understand and voluntarily sign an informed consent form
* Patients willing and able to undergo autologous and allogeneic transplantation
* no previous systemic therapy for the treatment of multiple myeloma (dexamethasone at a cumulative dose of 320 mg; plasmapheresis/dialysis without concomitant chemotherapy, local irradiation of bone lesions; and surgical intervention is accepted as pretreatment)
* Newly diagnosed multiple myeloma according to common diagnostic criteria including presence of CRAB and measurable disease parameters
* Cardiac ejection fraction (LVEF) of at least 50%
* Corrected DLCO of at least 50% ; alternatively pO2 \[art.\] of at least 70mmHg
* Karnofsky performance status of greater or equal to 50%
* adequate bone marrow function
* adequate serum chemistry values
* Use of adequate contraception for female subjects with childbearing potential and male subjects
* Bone marrow sample available for analysis of molecular cytogenetics
* Able to administer low molecular-weight heparin as a prophylactic anticoagulation therapy for the first three months(applicable for subjects randomized to RAD) and able to administer ASS 100 mg/d (applicable for subjects randomized to VRD)

Exclusion Criteria:

* Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
* Pregnant or lactating females
* Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk
* History of myocardial infarction; NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias; concomitant pericarditis or peri-/myocarditis
* Use of any other experimental drug or therapy within 28 days of baseline
* Greater or equal to Grade 2 peripheral neuropathy on clinical examination within 14 days before enrollment
* Known intolerance of boron
* Hypersensitivity to acyclovir or similar anti-viral drug
* Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer
* HIV positive, active hepatitis B, C or D viral infection, known CMV reactivation/active infection, EBV reactivation/active infection or treponema pallidum infection
* Uncontrolled diabetes mellitus
* Non-secretory MM
* Clinically relevant active infection or serious co-morbid medical conditions

Primary outcomes:
measure: The primary efficacy endpoint for the induction phase is the rate of patients with CR at first restaging
timeFrame: within 8 days after end of last induction cycle ((Day 92(RAD); Day 71(VRD))
measure: In the consolidation phase the primary efficacy endpoint for comparison II (response <VGPR after first ASCT) is the PFS rate
timeFrame: 3 years after the first ASCT, calculated from day 1 of ASCT.
Secondary outcomes:
measure: ORR following 3 cycles of induction treatment (VRD vs RAD)
timeFrame: within 8 days after end of last induction cycle
measure: CR and ORR at the end of the whole treatment programme
timeFrame: at the end of the whole treatment programme (approx. 8 years)
measure: Overall survival (OS)
timeFrame: 8 years from study entry
measure: Incidence, severity and relationship of SAEs
timeFrame: 30 days post last dosing of study drug
measure: Numbers of hospital stays and hospitalization days
timeFrame: within two years from second restaging
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen, Med. Klinik IV, Hämatologie u. Onkologie
city: Berg
country: Germany
facility: Schön Klinik Starnberger See, Hämatologie und Onkologie
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum, Hämatologie, Onkologie u. Tumorimmunologie
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte gGmbH, Klinik für Innere Medizin I
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik I
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen, Medizinische Klinik 5
city: Flensburg
country: Germany
facility: Malteser Krankenhaus St. Franziskus-Hospital, medizinische Klinik I
city: Frankfurt am Main
country: Germany
facility: Klinikum der Johann Woflgang Goethe Universität, Frankfurt am Mai
city: Frankfurt/Oder
country: Germany
facility: Klinikum Frankfurt (Oder) GmbH Medizinische Klinik I
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Abteilung für Innere Medizin I
city: Greifswald
country: Germany
facility: Universitätmedizin Greifswald, Klinik und Poliklinik für Innere Medizin C
city: Hamm
country: Germany
facility: St. Marien-Hospital gem. GmbHKna
city: Homburg/Saar
country: Germany
facility: Universitätsklinikum des Saarlandes Innere Medizin I
city: Jena
country: Germany
facility: Klinikum der Friedrich-Schiller-Universität Jena, Klinikum für Innrere Medizin II
city: Karlsruhe
country: Germany
facility: Städtisches Klinikum Karlsruhe Medizinische Klinik III, Abt. Hämatologie u. Onkologie
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Campus Kiel, II. Med. Poliklinik
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Medizinische Klinik und Poliklinik II im städtischen Krankenhaus Kiel
city: Koblenz
country: Germany
facility: Stiftungsklinikum Mittelrhein GmbH, Klinik für Innere Medizin
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Medizinische Klinik I
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim medizinische Klinik III
city: München
country: Germany
facility: Klinikum Schwabing
city: München
country: Germany
facility: Klinikum der Universität München-Großhadern
city: München
country: Germany
facility: III. Med. Klinik und Poliklinik, Klinikum rechts der Isar der TU München
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Medizinische Klinik u. Poliklinik A
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg Nord, 5. Medizinische LKinik, Onkologie/Hämatologie
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg GmbH, Klinik für Innere Medizin II
city: Regensburg
country: Germany
facility: Uniklinikum Regensburg, Abteilung für Hämatologie und internistische Onkologie
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus, Abt. Hämatologie, Onkologie u. Palliativmedizin
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm,Klinik für Innere Medizin III
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinkum Villingen-Schwennigen GmbH
city: Wiesbaden
country: Germany
facility: Dr. Horst Schmidt Kliniken, Klinik Innere Medizin III
city: Wuerzburg
country: Germany
facility: Universitätsklinikum Wuerzburg, Medizinische Klinik II
Study officials:
affiliation: Wuerzburg University Hospital
name: Stefan Knop, MD
role: STUDY_DIRECTOR
affiliation: Wuerzburg University Hospital
name: Hermann Einsele, MD
role: PRINCIPAL_INVESTIGATOR
References: