2006-32 Phase II Study of Rapidly Recycled High Dose DTPACE

This study has the following goals:

- To find out how many subjects treated with high dose DTPACE (Dexamethasone, Thalidomide,
CisPlatin, Adriamycin, Cyclophosphamide, and Etoposide. (HD DTPACE) on this protocol
will have a complete response or near complete response that lasts for 6 months or
longer.

- In subjects achieving a response, to find out how long the response will last.

- To learn more about the side effects of this treatment.

Up to 75 subjects, male or female, age 18 and older, regardless of race or ethnicity, will
participate in this study at the University of Arkansas for Medical Sciences (UAMS) only.

The treatment in this study is divided into 3 parts

- High dose DTPACE and stem cell collection if you do not already have sufficient stem
cells stored.

- High dose DTPACE and stem cell re-infusion.

- Velcade, Thalidomide, Dexamethasone (sometimes known as VTD) Maintenance therapy.

Inclusion Criteria:

- Patients with multiple myeloma, treated or untreated, with the presence of one or more
of the high risk features as defined below.

High risk by gene expression profiling at any time prior to enrollment:

1. PROLIFERATION signature, MMSET/FGFR3, c-MAF/MAF-B gene groups or

2. High risk score based on University of Arkansas Myeloma Institute for Research and
Therapy (MIRT) 70 gene model.

- Abnormal metaphase cytogenetics at any time prior to enrollment, or

- Lactate Dehydrogenase (LDH) > 250 IU/L (upper limit normal) at any time prior to
enrollment

- Zubrod ≤ 2, unless due to symptoms of MM.

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

- Patient must have signed an Institutional Review Board (IRB)-approved
informed consent and understand the investigational nature of the study.

- Negative serology for HIV.

- Patients must not have a history of chronic obstructive or chronic
restrictive pulmonary disease. Patients must have adequate pulmonary
function studies > 50% of predicted on mechanical aspects (FEV1, forced
vital capacity (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 echocardiogram (ECHO) or 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 left ventricular ejection fraction (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 HD-DTPACE, in the opinion of
the treating investigator, with the exception that patients with serum
creatinine > 1.5 mg/dL will receive modified doses of cisplatin.

Exclusion Criteria:

- Fever or active infection requiring intravenous antibiotics within 72 hours from
baseline.

- Liver function abnormalities with total bilirubin more than twice the upper limit of
normal or aspartate amino transferase (AST)/alanine amino trasferase (ALT) more than
three times the upper limit of normal.

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

- Platelet count < 30,000/mm3, or absolute neutrophil count (ANC) < 1,000/μl.

- 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.

- 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/m2.