2006-32 Phase II Study of Rapidly Recycled High Dose DTPACE
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: DTPACE
Intervention description: Dexamethasone 200 mg Intravenous Infusion "Piggy-Back" (IVPB) Days 1-7
Thalidomide 200 mg by mouth (PO) Days 1-7
Cisplatin 15mg/m2 Days 1-4 (modify for renal insufficiency)
Adriamycin 15 mg/m2 Days 1-4
Cyclophosphamide 600 mg/m2 Days 1-4
Etoposide 60 mg/m2 Days 1-4
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study is being done in an attempt to improve the remission rate and the survival time
      for subjects with high-risk myeloma. It is hoped that by giving higher doses of commonly used
      chemotherapy drugs and by giving courses closer together (before the myeloma comes back or
      gets worse), subjects in this study will have better outcomes.
    

Eligibility criteria:

        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.