Lenalidomide, Adriamycin, Dexamethasone (RAD) Versus Lenalidomide, Bortezomib, Dexamethasone (VRD) for Induction in Newly Diagnosed Multiple Myeloma Followed by Response-adapted Consolidation and Lenalidomide Maintenance

NCT ID: NCT01685814

Last Updated: 2023-04-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 406 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2023-12-31

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).

Conditions

Previously Untreated Symptomatic Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

single stem cell transplant, 3-year lenalidomide maintenance

Arm A

Group Type: ACTIVE_COMPARATOR

Lenalidomide, Bortezomib

Intervention Type: DRUG

Induction: two versus one novel drug maintenance: lenalidomide as a maintenance therapy

autologous stem cell transplant

Intervention Type: BIOLOGICAL

tandem autologous transplant, lenalidomide maintenance

Arm B

Group Type: EXPERIMENTAL

Lenalidomide, Bortezomib

Intervention Type: DRUG

Induction: two versus one novel drug maintenance: lenalidomide as a maintenance therapy

autologous stem cell transplant

Intervention Type: BIOLOGICAL

allogeneic stem cell transplant, lenalidomide maintenance

Arm C

Group Type: ACTIVE_COMPARATOR

Lenalidomide, Bortezomib

Intervention Type: DRUG

Induction: two versus one novel drug maintenance: lenalidomide as a maintenance therapy

autologous stem cell transplant

Intervention Type: BIOLOGICAL

allogeneic stem cell transplant

Intervention Type: BIOLOGICAL

tandem autologous transplant

Arm D

Group Type: EXPERIMENTAL

Lenalidomide, Bortezomib

Intervention Type: DRUG

Induction: two versus one novel drug maintenance: lenalidomide as a maintenance therapy

autologous stem cell transplant

Intervention Type: BIOLOGICAL

Interventions

Lenalidomide, Bortezomib

Induction: two versus one novel drug maintenance: lenalidomide as a maintenance therapy

Intervention Type: DRUG

autologous stem cell transplant

Intervention Type: BIOLOGICAL

allogeneic stem cell transplant

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ClinAssess GmbH

INDUSTRY

Sponsor Role: collaborator

Celgene Corporation

INDUSTRY

Sponsor Role: collaborator

Wuerzburg University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stefan Knop, MD

Role: STUDY_DIRECTOR

Wuerzburg University Hospital

Hermann Einsele, MD

Role: PRINCIPAL_INVESTIGATOR

Wuerzburg University Hospital

Locations

Universitätsklinikum Aachen, Med. Klinik IV, Hämatologie u. Onkologie

Aachen, , Germany

Schön Klinik Starnberger See, Hämatologie und Onkologie

Berg, , Germany

Charité Campus Virchow-Klinikum, Hämatologie, Onkologie u. Tumorimmunologie

Berlin, , Germany

Klinikum Bremen-Mitte gGmbH, Klinik für Innere Medizin I

Bremen, , Germany

Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik I

Dresden, , Germany

Universitätsklinikum Erlangen, Medizinische Klinik 5

Erlangen, , Germany

Malteser Krankenhaus St. Franziskus-Hospital, medizinische Klinik I

Flensburg, , Germany

Klinikum Frankfurt (Oder) GmbH Medizinische Klinik I

Frankfurt (Oder), , Germany

Klinikum der Johann Woflgang Goethe Universität, Frankfurt am Mai

Frankfurt am Main, , Germany

Universitätsklinikum Freiburg, Abteilung für Innere Medizin I

Freiburg im Breisgau, , Germany

Universitätmedizin Greifswald, Klinik und Poliklinik für Innere Medizin C

Greifswald, , Germany

St. Marien-Hospital gem. GmbHKna

Hamm, , Germany

Universitätsklinikum des Saarlandes Innere Medizin I

Homburg/Saar, , Germany

Klinikum der Friedrich-Schiller-Universität Jena, Klinikum für Innrere Medizin II

Jena, , Germany

Städtisches Klinikum Karlsruhe Medizinische Klinik III, Abt. Hämatologie u. Onkologie

Karlsruhe, , Germany

Universitätsklinikum Schleswig-Holstein Campus Kiel, II. Med. Poliklinik

Kiel, , Germany

Universitätsklinikum Schleswig-Holstein, Medizinische Klinik und Poliklinik II im städtischen Krankenhaus Kiel

Kiel, , Germany

Stiftungsklinikum Mittelrhein GmbH, Klinik für Innere Medizin

Koblenz, , Germany

Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Medizinische Klinik I

Lübeck, , Germany

Universitätsmedizin Mannheim medizinische Klinik III

Mannheim, , Germany

Klinikum Schwabing

München, , Germany

Klinikum der Universität München-Großhadern

München, , Germany

III. Med. Klinik und Poliklinik, Klinikum rechts der Isar der TU München

München, , Germany

Universitätsklinikum Münster, Medizinische Klinik u. Poliklinik A

Münster, , Germany

Klinikum Nürnberg Nord, 5. Medizinische LKinik, Onkologie/Hämatologie

Nuremberg, , Germany

Klinikum Oldenburg GmbH, Klinik für Innere Medizin II

Oldenburg, , Germany

Uniklinikum Regensburg, Abteilung für Hämatologie und internistische Onkologie

Regensburg, , Germany

Robert-Bosch-Krankenhaus, Abt. Hämatologie, Onkologie u. Palliativmedizin

Stuttgart, , Germany

Universitätsklinikum Ulm,Klinik für Innere Medizin III

Ulm, , Germany

Schwarzwald-Baar Klinkum Villingen-Schwennigen GmbH

Villingen-Schwenningen, , Germany

Dr. Horst Schmidt Kliniken, Klinik Innere Medizin III

Wiesbaden, , Germany

Universitätsklinikum Wuerzburg, Medizinische Klinik II

Würzburg, , Germany

Countries

Germany

Other Identifiers

2009-016616-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DSMM XIV

Identifier Type: -

Identifier Source: org_study_id