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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 ongoing, but not recruiting participants.
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: February 7, 2017
Last verified: February 2017
  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
Intervention Model: Parallel Assignment
Masking: No masking
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)) ]
  • 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. ]

Secondary Outcome Measures:
  • ORR following 3 cycles of induction treatment (VRD vs RAD) [ Time Frame: within 8 days after end of last induction cycle ]
  • CR and ORR at the end of the whole treatment programme [ Time Frame: at the end of the whole treatment programme (approx. 8 years) ]
  • Overall survival (OS) [ Time Frame: 8 years from study entry ]
  • Incidence, severity and relationship of SAEs [ Time Frame: 30 days post last dosing of study drug ]
  • Numbers of hospital stays and hospitalization days [ Time Frame: within two years from second restaging ]

Estimated Enrollment: 406
Study Start Date: May 2012
Estimated Study Completion Date: May 2020
Primary Completion Date: September 2016 (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   (Adult)
Sexes Eligible for Study:   All
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

Locations
Germany
Universitätsklinikum Aachen, Med. Klinik IV, Hämatologie u. Onkologie
Aachen, Germany, 52074
Schön Klinik Starnberger See, Hämatologie und Onkologie
Berg, Germany, 82335
Campus Virchow-Klinikum Charite´, Charite´- Centrum 14, Med. Klinik Hämatologie u. Onkologie
Berlin, Germany, 13353
Klinikum Bremen-Mitte gGmbH, Klinik für Innere Medizin I
Bremen, Germany, 28177
Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik I
Dresden, Germany, 01307
Universitätsklinikum Erlangen, Medizinische Klinik 5
Erlangen, Germany, 91054
Malteser Krankenhaus St. Franziskus-Hospital, medizinische Klinik I
Flensburg, Germany, 24939
Klinikum der Johann Woflgang Goethe Universität, Frankfurt am Mai
Frankfurt am Main, Germany, 60596
Klinikum Frankfurt (Oder) GmbH Medizinische Klinik I
Frankfurt/Oder, Germany, 15236
Universitätsklinikum Freiburg, Abteilung für Innere Medizin I
Freiburg, Germany, 79106
Universitätmedizin Greifswald, Klinik und Poliklinik für Innere Medizin C
Greifswald, Germany, 174751
St. Marien-Hospital gem. GmbHKna
Hamm, Germany, 59071
Universitätsklinikum des Saarlandes Innere Medizin I
Homburg/Saar, Germany, 66421
Klinikum der Friedrich-Schiller-Universität Jena, Klinikum für Innrere Medizin II
Jena, Germany, 07747
Städtisches Klinikum Karlsruhe Medizinische Klinik III, Abt. Hämatologie u. Onkologie
Karlsruhe, Germany, 76133
Universitätsklinikum Schleswig-Holstein Campus Kiel, II. Med. Poliklinik
Kiel, Germany, 24105
Universitätsklinikum Schleswig-Holstein, Medizinische Klinik und Poliklinik II im städtischen Krankenhaus Kiel
Kiel, Germany, 24116
Stiftungsklinikum Mittelrhein GmbH, Klinik für Innere Medizin
Koblenz, Germany, 56068
Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Medizinische Klinik I
Lübeck, Germany, 23538
Universitätsmedizin Mannheim medizinische Klinik III
Mannheim, Germany, 68167
Klinikum Schwabing
München, Germany, 80804
Klinikum der Universität München-Großhadern
München, Germany, 81366
III. Med. Klinik und Poliklinik, Klinikum rechts der Isar der TU München
München, Germany, 81675
Universitätsklinikum Münster, Medizinische Klinik u. Poliklinik A
Münster, Germany, 48149
Klinikum Nürnberg Nord, 5. Medizinische LKinik, Onkologie/Hämatologie
Nürnberg, Germany, 90419
Klinikum Oldenburg GmbH, Klinik für Innere Medizin II
Oldenburg, Germany, 26133
Klinikum Ernst von Bergmann, Klinik für Hämatologie, Onkologie
Potsdam, Germany, 14467
Uniklinikum Regensburg, Abteilung für Hämatologie und internistische Onkologie
Regensburg, Germany, 93053
Klinikum Stuttgart, Katharinenhospital
Stuttgart, Germany, 70174
Robert-Bosch-Krankenhaus, Abt. Hämatologie, Onkologie u. Palliativmedizin
Stuttgart, Germany, 70376
Universitätsklinikum Ulm,Klinik für Innere Medizin III
Ulm, Germany, 89081
Schwarzwald-Baar Klinkum Villingen-Schwennigen GmbH
Villingen-Schwenningen, Germany, 78048
Dr. Horst Schmidt Kliniken, Klinik Innere Medizin III
Wiesbaden, Germany, 65199
Universitätsklinikum Wuerzburg, Medizinische Klinik II
Wuerzburg, Germany, 97080
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

Responsible Party: Wuerzburg University Hospital
ClinicalTrials.gov Identifier: NCT01685814     History of Changes
Other Study ID Numbers: DSMM XIV
2009-016616-21 ( EudraCT Number )
Study First Received: June 27, 2012
Last Updated: February 7, 2017

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
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Liposomal doxorubicin
Thalidomide
Bortezomib
Doxorubicin
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on April 21, 2017