Randomized Trial of Lenalidomide, Bortezomib, Dexamethasone vs High-Dose Treatment With SCT in MM Patients up to Age 65
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Lenalidomide; Bortezomib; Dexamethasone; Autologous Stem Cell Transplant
Intervention description: oral administration; intravenous or, following protocol amendment, subcutaneous administration; oral administration
Dose of 20 mg/day for first 3 cycles. Dose of 10 mg/day for remaining cycles.; Autologous refers to stem cells that are harvested from the participant to be a source of new blood cells after high-dose chemotherapy with melphalan.
Intervention MeSH terms: Dexamethasone; Lenalidomide; Bortezomib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 729.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Lenalidomide; Bortezomib; Dexamethasone; Stem Cell Transplant; Myeloma; Multiple Myeloma

Summary:

      In this research study, we are looking to explore the drug combination, lenalidomide,
      bortezomib and dexamethasone alone or when combined with autologous stem cell transplantation
      to see what side effects it may have and how well it works for treatment of newly diagnosed
      multiple myeloma. Specifically, the objective of this trial is to determine if, in the era of
      novel drugs, high dose therapy (HDT) is still necessary in the initial management of multiple
      myeloma in younger patients. In this study, HDT as compared to conventional dose treatment
      would be considered superior if it significantly prolongs progression-free survival by at
      least 9 months or more, recognizing that particular subgroups may benefit more compared to
      others.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of Multiple Myeloma, according to the International Myeloma Foundation 2003
             Diagnostic Criteria

          -  Documented symptomatic myeloma, with organ damage related to myeloma with laboratory
             assessments performed within 21 days of registration

          -  Myeloma that is measurable by either serum or urine evaluation of the monoclonal
             component or by assay of serum free light chains.

          -  ECOG performance status </= 2

          -  Negative HIV blood test

          -  Voluntary written informed consent

        Exclusion Criteria:

          -  Pregnant or lactating female

          -  Prior systemic therapy for MM (localized radiotherapy allowed if at least 7 days
             before study entry, corticosteroids allowed if dose </= equivalent of 160 mg
             dexamethasone over 2 weeks)

          -  Primary amyloidosis (AL) or myeloma complicated by amylosis

          -  Receiving any other investigational agents

          -  Known brain metastases

          -  Poor tolerability or allergy to any of the study drugs or compounds of similar
             composition

          -  Platelet count <50,000/mm3, within 21 days of registration

          -  ANC <1,000 cells/mm3, within 21 days of registration

          -  Hemoglobin <8 g/dL, within 21 days of registration

          -  Hepatic impairment (>/= 1.5 x institutional ULN or AST (SGOT), ALT (SGPT), or alkaline
             phosphatase >2 x ULN). Patients with benign hyperbilirubinemia are eligible.

          -  Renal insufficiency (serum creatinine >2.0 mg/dl or creatinine clearance <50 ml/min,
             within 21 days of registration)

          -  Respiratory compromise (DLCO < 50%)

          -  Clinical signs of heart or coronary failure or LVEF < 40%. Myocardial infarction
             within 6 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled
             angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
             of acute ischemia or active conductive system abnormalities

          -  Intercurrent illness including, but not limited to ongoing or active severe infection,
             known infection with hepatitis B or C virus, poorly controlled diabetes, severe
             uncontrolled psychiatric disorder or psychiatric illness/social situations that would
             limit compliance with study requirements

          -  Previous history of another malignant condition except for basal cell carcinoma and
             stage I cervical cancer. If malignancy was experienced more than 2 years ago and
             confirmed as cured, these participants may be considered for the study on case by case
             basis with PI discussion.

          -  Inability to comply with an anti-thrombotic treatment regimen

          -  Peripheral neuropathy >/= Grade 2