Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00003967

Trial Description

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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

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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).

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Brief Summary in Scientific Language

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Organizational Data

  •   DRKS00003967
  •   2012/11/20
  •   2012/06/27
  •   yes
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Secondary IDs

  •   2009-016616-21 
  •   NCT01685814  (ClinicalTrials.gov)
  •   DSMM XIV  (Wuerzburg University Hospital)
  •   2009-016616-21 
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Health Condition or Problem studied

  •   Previously Untreated Symptomatic Multiple Myeloma
  •   C90.0 -  Multiple myeloma
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Interventions/Observational Groups

  •   Drug: Lenalidomide, Bortezomib
  •   Biological: autologous stem cell transplant
  •   Biological: allogeneic stem cell transplant
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   III
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Primary Outcome

- 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.

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Secondary Outcome

- 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

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

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  •   2012/05/31
  •   406
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   65   Years
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Additional 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)

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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

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Addresses

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    • Wuerzburg University Hospital
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    • ClinAssess GmbH
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    • Celgene Corporation
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    • Wuerzburg University Hospital
    • Stefan Knop, MD 
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    • Stefan Knop, MD 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   364
  •   2013/10/30
* This entry means the parameter is not applicable or has not been set.