Study of Multiple Myeloma Patients Relapsing or Progressing After Autologous Transplantation on Total Therapy 2
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Velcade, Thalidomide, and Dexamethasone; Velcade, Melphalan, and Dexamethasone
Intervention description: Velcade - Into vein (IV) Days 1, 4, 8, 11
Yr 1: Every 28-35 days-12 cycles
Yr 2: Every 8-10 weeks- 6 cycles
Thalidomide - By Mouth Days 1-28
Yr 1: Every 28-35 days-12 cycles
Yr 2: Every 8-10 weeks- 6 cycles; Velcade - Into vein (IV) Days 1, 4, 8, 11
Yr 1: Every 28-35 days-12 cycles
Yr 2: Every 8-10 weeks- 6 cycles
Intervention MeSH terms: Thalidomide; Dexamethasone; Dexamethasone acetate; Melphalan; Bortezomib; BB 1101
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study is being done to find out if the combination of VelcadeTM with melphalan and
      dexamethasone (VMD) will be as effective, or even more effective as it is in combination with
      thalidomide and dexamethasone (VTD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  History of histologically documented MM previously enrolled on UARK 98-026 with
             relapsed or progressive disease after at least one autologous transplant.

          -  Patient has measurable disease in which to capture response, defined as:

          -  Serum M-protein level > 1.0 gm/dl (10.0 g/L) measured by serum protein electrophoresis
             or immunoglobulin electrophoresis

          -  Urinary M-protein excretion > 200 mg/24 hrs

          -  Bone marrow plasmacytosis of > 30percent by bone marrow aspirate and/or biopsy

          -  Serum Free Light Chains (By the Freelite test) > 10 mg/dL with an abnormal
             kappa/lambda ration.

          -  50percent increase in size of lytic and/or focal lesions or development of new lesions
             recognized by radiographic studies.

          -  Performance status of 2 as per SWOG scale, unless PS of 3-4 based solely on bone pain.

          -  Patients must have a platelet count 50,000/mm3, unless the low platelet count is due
             to documented (>30 percent) extensive myeloma infiltration of the bone marrow.

          -  Patients must have adequate renal function defined as serum creatinine < 2.5 mg/dl.

          -  Patients must have adequate hepatic function defined as serum transaminases and direct
             bilirubin < 2 x the upper limit of normal.

          -  Pregnant or nursing women may not participate. Women of childbearing potential must
             have a negative pregnancy documented within one week of registration. Women of
             reproductive potential may not participate unless they have agreed to use an effective
             contraceptive method.

          -  Male or female adults of at least 18 years of age.

          -  Patients must have signed and IRB-approved written informed consent form and
             demonstrate willingness to meet follow-up schedule and study procedure obligations

          -  > 5 x 106 CD34 cells/kg in storage strongly desired, but not mandated

        Exclusion Criteria:

          -  Not previously enrolled on UARK 98-026.

          -  Has received salvage therapy after coming off UARK 98-026.

          -  Evidence of POEMS Syndrome..

          -  Significant neurotoxicity interfering with ADL.

          -  Platelet count < 50,000/mm3

          -  Clinically significant hepatic dysfunction as noted by bilirubin or AST >3 times the
             upper normal limit or clinically significant concurrent hepatitis.

          -  New York Hospital Association (NYHA) Class III or Class IV heart failure.

          -  Myocardial infarction within the last 6 months.

          -  Truly non-secretory MM (no increase in serum free-light chains) in the absence of bone
             marrow plasmacytosis and MRI-defined focal lesions with CT-FNA-proven MM

          -  Uncontrolled, active infection requiring IV antibiotics.

          -  Patients with a history of treatment for clinically significant ventricular cardiac
             arrhythmias.

          -  Poorly controlled hypertension, diabetes mellitus, or other serious or psychiatric
             illness that could potentially interfere with the completion of treatment according to
             this protocol.

          -  Pregnant or potential for pregnancy. Women of childbearing potential will have a
             pregnancy test at screening, and will be required to use a medically approved
             contraceptive method. Pregnancy testing will be performed prior to administration of
             each dose of study drug.

          -  Breast-feeding women may not participate.