Previously Untreated Symptomatic Multiple Myeloma
Conditions
Keywords
multiple myeloma, autologous stem cell transplant, allogeneic stem cell transplant, lenalidomide, bortezomib
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).
Interventions
Induction: two versus one novel drug maintenance: lenalidomide as a maintenance therapy
BIOLOGICALautologous stem cell transplant
BIOLOGICALallogeneic stem cell transplant
Sponsors
ClinAssess GmbH
Celgene Corporation
Wuerzburg University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Overall survival (OS) | 8 years from study entry |
| ORR following 3 cycles of induction treatment (VRD vs RAD) | within 8 days after end of last induction cycle |
| Numbers of hospital stays and hospitalization days | within two years from second restaging |
| Incidence, severity and relationship of SAEs | 30 days post last dosing of study drug |
| CR and ORR at the end of the whole treatment programme | at the end of the whole treatment programme (approx. 8 years) |
Countries
Germany
Outcome results
None listed