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

NCT01685814 | Unknown Phase 3

• 2 other identifiers: DSMM XIV2009-016616-21
• Study Type: interventional
• Target: 406
• Locations: 1 country
• Sites: 32

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

Keywords

multiple myeloma; autologous stem cell transplant; allogeneic stem cell transplant; lenalidomide; bortezomib

Outcome Measures

Primary Outcomes (2)

• The primary efficacy endpoint for the induction phase is the rate of patients with CR at first restaging

  within 8 days after end of last induction cycle ((Day 92(RAD); Day 71(VRD))

• In the consolidation phase the primary efficacy endpoint for comparison II (response <VGPR after first ASCT) is the PFS rate

  3 years after the first ASCT, calculated from day 1 of ASCT.

Secondary Outcomes (5)

• ORR following 3 cycles of induction treatment (VRD vs RAD)

  within 8 days after end of last induction cycle

• CR and ORR at the end of the whole treatment programme

  at the end of the whole treatment programme (approx. 8 years)

• Overall survival (OS)

  8 years from study entry

• Incidence, severity and relationship of SAEs

  30 days post last dosing of study drug

• Numbers of hospital stays and hospitalization days

  within two years from second restaging

Study Arms (4)

single stem cell transplant, 3-year lenalidomide maintenance

ACTIVE COMPARATOR

Arm A

Drug: Lenalidomide, Bortezomib; Biological: autologous stem cell transplant

tandem autologous transplant, lenalidomide maintenance

EXPERIMENTAL

Arm B

Drug: Lenalidomide, Bortezomib; Biological: autologous stem cell transplant

allogeneic stem cell transplant, lenalidomide maintenance

ACTIVE COMPARATOR

Arm C

Drug: Lenalidomide, Bortezomib; Biological: autologous stem cell transplant; Biological: allogeneic stem cell transplant

tandem autologous transplant

EXPERIMENTAL

Arm D

Drug: Lenalidomide, Bortezomib; Biological: autologous stem cell transplant

Interventions

Lenalidomide, Bortezomib DRUG

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

allogeneic stem cell transplant, lenalidomide maintenance; single stem cell transplant, 3-year lenalidomide maintenance; tandem autologous transplant; tandem autologous transplant, lenalidomide maintenance

autologous stem cell transplant BIOLOGICAL

allogeneic stem cell transplant, lenalidomide maintenance; single stem cell transplant, 3-year lenalidomide maintenance; tandem autologous transplant; tandem autologous transplant, lenalidomide maintenance

allogeneic stem cell transplant BIOLOGICAL

allogeneic stem cell transplant, lenalidomide maintenance

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Wuerzburg University Hospital: lead
• ClinAssess GmbH: collaborator
• Celgene Corporation: collaborator

Study Sites (32)

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

Aachen, 52074, Germany

Location

Schön Klinik Starnberger See, Hämatologie und Onkologie

Berg, 82335, Germany

Location

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

Berlin, 13353, Germany

Location

Klinikum Bremen-Mitte gGmbH, Klinik für Innere Medizin I

Bremen, 28177, Germany

Location

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

Dresden, 01307, Germany

Location

Universitätsklinikum Erlangen, Medizinische Klinik 5

Erlangen, 91054, Germany

Location

Malteser Krankenhaus St. Franziskus-Hospital, medizinische Klinik I

Flensburg, 24939, Germany

Location

Klinikum Frankfurt (Oder) GmbH Medizinische Klinik I

Frankfurt (Oder), 15236, Germany

Location

Klinikum der Johann Woflgang Goethe Universität, Frankfurt am Mai

Frankfurt am Main, 60596, Germany

Location

Universitätsklinikum Freiburg, Abteilung für Innere Medizin I

Freiburg im Breisgau, 79106, Germany

Location

Universitätmedizin Greifswald, Klinik und Poliklinik für Innere Medizin C

Greifswald, 17475, Germany

Location

St. Marien-Hospital gem. GmbHKna

Hamm, 59071, Germany

Location

Universitätsklinikum des Saarlandes Innere Medizin I

Homburg/Saar, 66421, Germany

Location

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

Jena, 07747, Germany

Location

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

Karlsruhe, 76133, Germany

Location

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

Kiel, 24105, Germany

Location

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

Kiel, 24116, Germany

Location

Stiftungsklinikum Mittelrhein GmbH, Klinik für Innere Medizin

Koblenz, 56068, Germany

Location

Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Medizinische Klinik I

Lübeck, 23538, Germany

Location

Universitätsmedizin Mannheim medizinische Klinik III

Mannheim, 68167, Germany

Location

Klinikum Schwabing

München, 80804, Germany

Location

Klinikum der Universität München-Großhadern

München, 81366, Germany

Location

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

München, 81675, Germany

Location

Universitätsklinikum Münster, Medizinische Klinik u. Poliklinik A

Münster, 48149, Germany

Location

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

Nuremberg, 90419, Germany

Location

Klinikum Oldenburg GmbH, Klinik für Innere Medizin II

Oldenburg, 26133, Germany

Location

Uniklinikum Regensburg, Abteilung für Hämatologie und internistische Onkologie

Regensburg, 93053, Germany

Location

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

Stuttgart, 70376, Germany

Location

Universitätsklinikum Ulm,Klinik für Innere Medizin III

Ulm, 89081, Germany

Location

Schwarzwald-Baar Klinkum Villingen-Schwennigen GmbH

Villingen-Schwenningen, 78048, Germany

Location

Dr. Horst Schmidt Kliniken, Klinik Innere Medizin III

Wiesbaden, 65199, Germany

Location

Universitätsklinikum Wuerzburg, Medizinische Klinik II

Würzburg, 97080, Germany

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines

Study Officials

• Stefan Knop, MD

  Wuerzburg University Hospital

  STUDY DIRECTOR

• Hermann Einsele, MD

  Wuerzburg University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2012
• First Posted: September 14, 2012
• Study Start: May 1, 2012
• Primary Completion: September 1, 2016
• Study Completion: December 1, 2023
• Last Updated: April 27, 2023

Record last verified: 2023-04

Locations

DE (32)