A Phase III Study for Patients Relapsing or Progressing After Autologous Transplantation on Total Therapy 2 (TT2, UARK 98-026): Bortezomib, Thalidomide and Dexamethasone Versus Bortezomib, Melphalan, and Dexamethasone
- 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
- 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
- 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
- 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
- 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.