A Phase II Randomized Study Comparing Two Doses of Carfilzomib (NSC-756640) with Dexamethasone for Multiple Myeloma Patients with Relapsed or Refractory Disease

-Pts must have symptomatic MM, and be relapsed or refractory.
-Pts must have measurable disease within 28 days prior to reg.
-Pts must have received at least one prior regimen of chemo for symptomatic MM. Pts may not have more than 6 previous regimens of therapy for the disease; prior chemo must have been completed at least 28 days prior to reg.
-Pts may not have received any prior carfilzomib.
-Pts must not be receiving any other concurrent investigational therapy. Pts must not be planning to receive any radiotherapy (except localized radiation for palliative care). Pts must not be planning to receive any concurrent chemo, immunotherapy, radiotherapy or other treatment with curative intent.
-Pts must have complete history and physical examination within 28 days prior to reg.
-Pts must have baseline PET scan within 28 days prior to reg. Note that images are submitted centrally for review.
-Pts with non-secretory MM or known primary amyloidosis are not eligible.
-Pts must be >/= 18 years of age.
j. Patients must have Zubrod Performance Status 0-2.
-Pts must not have clinically significant illness including uncontrolled, active infection requiring IV antibiotics, NYHA Class III or Class IV heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or >/= Grade 3 cardiac arrhythmias.
-Pts must have undergone an EKG within 28 days prior to reg.
-Pts must have an ECHO with ejection fraction >/= 45% within 28 days prior to reg.
-Pts must not have > Grade 2 neuropathy and/or POEMS syndrome.
-Pts must have adequate liver function as evidenced by total bilirubin </= 1.5 x(UL) and SGOT and SGPT </= 3 x ULN within 14 days prior to reg.
-Pts must have adequate bone marrow function as defined by the following within 14 days prior to registration: ANC ≥ 1,000 cell/mm3 without growth factor support, AND platelets >/= 50,000 cells/mm3 for patients who have bone marrow plasmacytosis < 50% or >/= 30,000 cells/mm3 for patients who have bone marrow plasmacytosis of >/= 50%.
-Pts must have calculated or measured creatinine clearance >/= 30 ml/min within 14 days prior to reg.
-Pts who are known to be HIV+ are eligible providing they meet all of the following additional criteria within 28 days prior to reg: � CD4 cells ≥ 500/mm3, � Viral load of < 50 copies HIV RNA/mm3 if on cART or < 25,000 copies HIV mRNA if not on cART, � No zidovudine or stavudine as part of cART
Patients who are HIV+ and do not meet all of these criteria are not eligible for this study.
-Pts with known Hep B or Hep C infection must have viral load < 800,000 IU/L within 28 days prior to reg.
-Pts must have baseline skeletal survey to document lytic lesions, osteopenia or compression fracture within 28 days prior to reg.
-Pts must be off myelosuppressive chemotherapy and non-myelosuppressive chemotherapy and XRT for >/= 2 8 days (>/= 6 weeks for nitrosoureas) and must have recovered to </= Grade 1 from all treatment associated toxicities prior to reg. Pts are allowed to have treatment for up to 7 days with pulse steroids for a myeloma-related complication prior to registration, as considered necessary by the treating physician.
-Pts must be offered participation in specimen submission for translational medicine studies and banking. With patient consent, specimens must be submitted as outlined.
Pts must not be pregnant or nursing due to the teratogenic nature of the study drugs. Women/men of reproductive potential must have agreed to use an effective contraceptive method.
- No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.
-Pts or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.