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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by Wuerzburg University Hospital
Sponsor:
Collaborators:
ClinAssess GmbH
Celgene Corporation
Information provided by (Responsible Party):
Wuerzburg University Hospital
ClinicalTrials.gov Identifier:
NCT01685814
First received: June 27, 2012
Last updated: September 11, 2012
Last verified: September 2012
  Purpose

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).


Condition Intervention Phase
Previously Untreated Symptomatic Multiple Myeloma
Drug: Lenalidomide, Bortezomib
Biological: autologous stem cell transplant
Biological: allogeneic stem cell transplant
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Wuerzburg University Hospital:

Primary Outcome Measures:
  • The primary efficacy endpoint for the induction phase is the rate of patients with CR at first restaging [ Time Frame: within 8 days after end of last induction cycle ((Day 92(RAD); Day 71(VRD)) ] [ Designated as safety issue: No ]
  • In the consolidation phase the primary efficacy endpoint for comparison II (response <VGPR after first ASCT) is the PFS rate [ Time Frame: 3 years after the first ASCT, calculated from day 1 of ASCT. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ORR following 3 cycles of induction treatment (VRD vs RAD) [ Time Frame: within 8 days after end of last induction cycle ] [ Designated as safety issue: No ]
  • CR and ORR at the end of the whole treatment programme [ Time Frame: at the end of the whole treatment programme (approx. 8 years) ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: 8 years from study entry ] [ Designated as safety issue: No ]
  • Incidence, severity and relationship of SAEs [ Time Frame: 30 days post last dosing of study drug ] [ Designated as safety issue: Yes ]
  • Numbers of hospital stays and hospitalization days [ Time Frame: within two years from second restaging ] [ Designated as safety issue: No ]

Estimated Enrollment: 406
Study Start Date: May 2012
Estimated Study Completion Date: May 2020
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: single stem cell transplant, 3-year lenalidomide maintenance
Arm A
Drug: Lenalidomide, Bortezomib
Induction: two versus one novel drug maintenance: lenalidomide as a maintenance therapy
Biological: autologous stem cell transplant
Experimental: tandem autologous transplant, lenalidomide maintenance
Arm B
Drug: Lenalidomide, Bortezomib
Induction: two versus one novel drug maintenance: lenalidomide as a maintenance therapy
Biological: autologous stem cell transplant
Active Comparator: allogeneic stem cell transplant, lenalidomide maintenance
Arm C
Drug: Lenalidomide, Bortezomib
Induction: two versus one novel drug maintenance: lenalidomide as a maintenance therapy
Biological: autologous stem cell transplant Biological: allogeneic stem cell transplant
Experimental: tandem autologous transplant
Arm D
Drug: Lenalidomide, Bortezomib
Induction: two versus one novel drug maintenance: lenalidomide as a maintenance therapy
Biological: autologous stem cell transplant

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01685814

Contacts
Contact: Stefan Knop, MD +49-931-201-0 dsmm@klinik.uni-wuerzburg.de

Locations
Germany
Universitätsklinikum Aachen, Med. Klinik IV, Hämatologie u. Onkologie Not yet recruiting
Aachen, Germany, 52074
Contact: Tim Brümmendorf, MD    (0049) 241/80-89805      
Principal Investigator: Tim Brümmendorf, MD         
Schön Klinik Starnberger See, Hämatologie und Onkologie Not yet recruiting
Berg, Germany, 82335
Contact: Christian Straka, MD    (0049)-8151-17817      
Principal Investigator: Christian Straka, MD         
Campus Virchow-Klinikum Charite´, Charite´- Centrum 14, Med. Klinik Hämatologie u. Onkologie Not yet recruiting
Berlin, Germany, 13353
Contact: Isrid Sturm, MD    (0049) 30-450-553302      
Principal Investigator: Isrid Sturm, MD         
Klinikum Bremen-Mitte gGmbH, Klinik für Innere Medizin I Not yet recruiting
Bremen, Germany, 28177
Contact: Bernd Hertenstein, MD    (0049)-421-4975240      
Principal Investigator: Bernd Hertenstein, MD         
Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik I Not yet recruiting
Dresden, Germany, 01307
Contact: Christoph Röllig, MD    (0049)-351-45813775      
Principal Investigator: Christoph Röllig, MD         
Universitätsklinikum Erlangen, Medizinische Klinik 5 Not yet recruiting
Erlangen, Germany, 91054
Contact: Wolf Rösler, MD    (0049) 9131-85-35954      
Principal Investigator: Wolf Rösler, MD         
Malteser Krankenhaus St. Franziskus-Hospital, medizinische Klinik I Recruiting
Flensburg, Germany, 24939
Contact: Nadezda Basara, MD    (0049) 461/816-2512      
Principal Investigator: Nadezda Basara, MD         
Klinikum der Johann Woflgang Goethe Universität, Frankfurt am Mai Not yet recruiting
Frankfurt am Main, Germany, 60596
Contact: Ivana von Metzler, MD    (0049) 69 / 6301-0      
Principal Investigator: Ivana von Metzler, MD         
Klinikum Frankfurt (Oder) GmbH Medizinische Klinik I Not yet recruiting
Frankfurt/Oder, Germany, 15236
Contact: Michael Kiehl, MD    (0049) 335-548-4600      
Principal Investigator: Michael Kiehl, MD         
Universitätsklinikum Freiburg, Abteilung für Innere Medizin I Recruiting
Freiburg, Germany, 79106
Contact: Monika Engelhardt, MD    (0049)-761-27032460      
Principal Investigator: Monika Engelhardt, MD         
Universitätmedizin Greifswald, Klinik und Poliklinik für Innere Medizin C Not yet recruiting
Greifswald, Germany, 174751
Contact: Gotfried Dölken, MD    (0049)-3834-866698      
Principal Investigator: Gottfried Dölken, MD         
St. Marien-Hospital gem. GmbHKna Not yet recruiting
Hamm, Germany, 59071
Contact: Heinz Dürk, MD    (0049)-2381-182251      
Principal Investigator: Heinz Dürk, MD         
Universitätsklinikum des Saarlandes Innere Medizin I Not yet recruiting
Homburg/Saar, Germany, 66421
Contact: Michael Preundschuh, MD    (0049)-6841-162-3002      
Principal Investigator: Michael Preundschuh, MD         
Klinikum der Friedrich-Schiller-Universität Jena, Klinikum für Innrere Medizin II Recruiting
Jena, Germany, 07747
Contact: Lars-Olof Mügge, MD    (0049) 3641/932-4570      
Principal Investigator: Lars-Olof Mügge, MD         
Städtisches Klinikum Karlsruhe Medizinische Klinik III, Abt. Hämatologie u. Onkologie Not yet recruiting
Karlsruhe, Germany, 76133
Contact: Mark Ringhoffer, MD    (0049) 721/974-3001      
Principal Investigator: Mark Ringhoffer, MD         
Universitätsklinikum Schleswig-Holstein, Medizinische Klinik und Poliklinik II im städtischen Krankenhaus Kiel Not yet recruiting
Kiel, Germany, 24116
Contact: Michael Kneba    (0049) 431/1697-1201      
Principal Investigator: Michael Kneba, MD         
Universitätsklinikum Schleswig-Holstein Campus Kiel, II. Med. Poliklinik Recruiting
Kiel, Germany, 24105
Contact: Martin Gramatzki, MD    (0049)-431-597-5802      
Principal Investigator: Martin Gramatzki, MD         
Stiftungsklinikum Mittelrhein GmbH, Klinik für Innere Medizin Not yet recruiting
Koblenz, Germany, 56068
Contact: Ralph Naumann, MD    (0049)-261-1377558      
Principal Investigator: Ralph Naumann, MD         
Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Medizinische Klinik I Recruiting
Lübeck, Germany, 23538
Contact: Harald Biersack, MD    (0049) 451/500-0      
Principal Investigator: Harry Biersack, MD         
Universitätsmedizin Mannheim medizinische Klinik III Not yet recruiting
Mannheim, Germany, 68167
Contact: Stefan Klein, MD    (0049) 621-383-4116      
Principal Investigator: Stefan Klein, MD         
Klinikum Schwabing Not yet recruiting
München, Germany, 80804
Contact: Clemens-Martin Wendtner, MD    (0049)-3068-2228      
Principal Investigator: Clemens-Martin Wendtner, MD         
Klinikum der Universität München-Großhadern Not yet recruiting
München, Germany, 81366
Contact: Helmut Ostermann, MD    (0049)-89-7095-6038      
Principal Investigator: Helmut Ostermann, MD         
III. Med. Klinik und Poliklinik, Klinikum rechts der Isar der TU München Recruiting
München, Germany, 81675
Contact: Florian Bassermann, MD    (0049) 89/4140-5038      
Principal Investigator: Florian Bassermann, MD         
Universitätsklinikum Münster, Medizinische Klinik u. Poliklinik A Not yet recruiting
Münster, Germany, 48149
Contact: Martin Kropff, MD    (0049)-251-8347590      
Principal Investigator: Martin Kropff, MD         
Klinikum Nürnberg Nord, 5. Medizinische LKinik, Onkologie/Hämatologie Not yet recruiting
Nürnberg, Germany, 90419
Contact: Kerstin Schäfer-Eckart, MD    (0049)-911-398-3650      
Principal Investigator: Kerstin Schäfer-Eckart, MD         
Klinikum Oldenburg GmbH, Klinik für Innere Medizin II Recruiting
Oldenburg, Germany, 26133
Contact: Bernd Metzner, MD    (0049)-441-403-2614      
Principal Investigator: Bernd Metzner, MD         
Klinikum Ernst von Bergmann, Klinik für Hämatologie, Onkologie Not yet recruiting
Potsdam, Germany, 14467
Contact: Georg Maschmeyer, MD    (0049) 0331/241-0      
Principal Investigator: Georg Maschmeyer, MD         
Uniklinikum Regensburg, Abteilung für Hämatologie und internistische Onkologie Not yet recruiting
Regensburg, Germany, 93053
Contact: Albrecht Reichle    (0049)-941-944-5541      
Principal Investigator: Albrecht Reichle, MD         
Klinikum Stuttgart, Katharinenhospital Not yet recruiting
Stuttgart, Germany, 70174
Contact: Hans-Guenther Mergenthaler, MD    (0049)-711-278-35601      
Principal Investigator: Hans-Günther Mergenthaler, MD         
Robert-Bosch-Krankenhaus, Abt. Hämatologie, Onkologie u. Palliativmedizin Not yet recruiting
Stuttgart, Germany, 70376
Contact: Martin Kaufmann, MD    (0049) 711/8101-0      
Principal Investigator: Martin Kaufmann, MD         
Universitätsklinikum Ulm,Klinik für Innere Medizin III Recruiting
Ulm, Germany, 89081
Contact: Christian Langer, MD    (00749) 31-500-45743      
Principal Investigator: Christian Langer, MD         
Schwarzwald-Baar Klinkum Villingen-Schwennigen GmbH Recruiting
Villingen-Schwenningen, Germany, 78048
Contact: Wolfram Brugger, MD    (0049) 7721/93-4001      
Principal Investigator: Wolfram Brugger, MD         
Dr. Horst Schmidt Kliniken, Klinik Innere Medizin III Not yet recruiting
Wiesbaden, Germany, 65199
Contact: Norbert Frickhofen, MD    (0049) 611 433018      
Principal Investigator: Norbert Frickhofen, MD         
Universitätsklinikum Wuerzburg, Medizinische Klinik II Not yet recruiting
Wuerzburg, Germany, 97080
Contact: Hermann Einsele, MD    (0049)-931-201-40001      
Principal Investigator: Hermann Einsele, MD         
Sponsors and Collaborators
Wuerzburg University Hospital
ClinAssess GmbH
Celgene Corporation
Investigators
Study Director: Stefan Knop, MD Wuerzburg University Hospital
Principal Investigator: Hermann Einsele, MD Wuerzburg University Hospital
  More Information

No publications provided

Responsible Party: Wuerzburg University Hospital
ClinicalTrials.gov Identifier: NCT01685814     History of Changes
Other Study ID Numbers: DSMM XIV, 2009-016616-21
Study First Received: June 27, 2012
Last Updated: September 11, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Wuerzburg University Hospital:
multiple myeloma
autologous stem cell transplant
allogeneic stem cell transplant
lenalidomide
bortezomib

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents

ClinicalTrials.gov processed this record on November 27, 2014