UARK 2006-32: Phase II Study of Rapidly Recycled High Dose DTPACE (HD-DTPACE) for Untreated or Previously Treated, High-Risk Multiple Myeloma (MM)

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 groups or

2. High risk score based on MIRT 70 gene model.

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

- 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 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, 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 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 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 AST/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 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.