UARK 2006-15: A Phase III Randomized Study of Tandem Transplants With or Without Bortezomib (Velcade) and Thalidomide (Thalomid) to Evaluate Its Effect on Response Rate and Durability of Response in Multiple Myeloma Patients

Inclusion Criteria:

- Patients with symptomatic multiple myeloma, sensitive or refractory to at least one
prior line of chemotherapy.

- Karnofsky performance score > 60%, unless due to MM.

- Patients must be <75 years of age at the time of registration.

- Patient must not have had a prior auto- or allotransplant.

- Patient must have signed an IRB-approved informed consent and understand the
investigational nature of the study.

- Negative serology for HIV.

- Baseline biopsies and laboratory studies are to be completed within 35 days of
registration, within 60 days for scans and radiological studies; patients must not
have a history of severe chronic obstructive or chronic restrictive pulmonary
disease. Patients must have adequate pulmonary function studies > 50% of predicted
on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > 50% of
predicted. Patients unable to complete pulmonary function tests because of
myeloma-related chest pain, must have a high resolution CT scan of the chest and must
also have acceptable arterial blood gases defined as P02 greater than 70.

- Patients with recent (< 6 months) myocardial infarction, unstable angina, difficult
to control congestive heart failure, uncontrolled hypertension, or difficult to
control cardiac arrhythmias are ineligible. Ejection fraction by ECHO or MUGA must
be > 40% and must be performed within 60 days prior to registration, unless the
patient has received chemotherapy within that period of time (dexamethasone and
thalidomide excluded), in which case the LVEF must be repeated.

- No prior malignancy is allowed except for adequately treated basal cell or squamous
cell skin cancer, in situ cervical cancer, or other cancer for which the patient has
been disease free for at least three years. Prior malignancy is acceptable provided
there has been no evidence of disease within the three-year interval or if the
malignancy is considered much less life threatening than the myeloma.

- Pregnant or nursing women may not participate. Women of childbearing potential must
have a negative pregnancy documented within one week of registration. Women/men of
reproductive potential may not participate unless they have agreed to use an
effective contraceptive method.

- Patients must be able to receive full doses of D PACE, in the opinion of the treating
investigator, with the exception that patients with creatinine clearance 30-50 ml/min
will receive only 50% of the cisplatin dose.

Exclusion Criteria:

- Fever or active infection requiring intravenous antibiotic, defined as fever or
antibiotics within 72 hours from baseline.

- Severe renal dysfunction, defined as a creatinine > 3mg/dl or a creatinine clearance
of < 30ml/min.

- Significant neurotoxicity, defined as grade > 3 neurotoxicity per NCI Common Toxicity
Criteria (See Appendix).

- Platelet count < 100,000/mm^3, or ANC < 1,000/μl

- POEMS Syndrome.

- Clinically significant hepatic dysfunction as noted by direct 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.

- Patients with a history of treatment for clinically significant ventricular cardiac
arrhythmias.

- Poorly-controlled hypertension, diabetes mellitus, or other serious medical illness
or psychiatric illness that could potentially interfere with the completion of
treatment according to this protocol.

- Prior adriamycin exposure >450 mg/m^2

- Prior exposure to thalidomide which resulted in severe toxicity requiring drug
discontinuation.