Vorinostat, Bortezomib, and Doxorubicin Hydrochloride Liposome in Treating Patients With Relapsed or Refractory Multiple Myeloma

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma

  • Relapsed or refractory disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 3 months
• ANC ≥ 1.0 x 10^9/L (no granulocyte growth factor support, e.g., G-CSF or GM-CSF allowed)
• Platelet count ≥ 100 x 10^9/L (erythropoietin allowed, no platelet or RBC transfusion within the past 2 weeks)
• Hemoglobin ≥ 8 g/dL (erythropoietin allowed, no platelet or RBC transfusion within the past 2 weeks)
• Creatinine clearance ≥ 30 mL/min
• AST or ALT ≤ 2.5 times upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• LVEF ≥ 45% by MUGA or ECHO
• Symptomatic neuropathy < grade 2
• No known history of HIV
• No active or serious infection, medical or psychiatric illness that would preclude study participation
• No active hepatitis B or C infection
• No other prior or concurrent malignancy except for adequately treated basal cell or squamous cell carcinoma of the skin, in situ malignancy, low-risk prostate cancer after curative therapy, or other cancer for which the patient has been disease-free for ≥ 3 years
• No history of hypersensitivity reaction to bortezomib or any of its components (boron, mannitol), vorinostat, doxorubicin hydrochloride, or any of the components of PLD
• No serum potassium ≤ 3.0 or serum magnesium ≤ 1.6 that cannot be corrected with supplementation are excluded

• Patients must have adequate cardiovascular function, defined by all of the following:

  • No EKG evidence of active, clinically significant conduction system abnormalities
  • No EKG evidence of QTc prolongation > grade 2
• NOTE: Any EKG abnormality at screening has to be documented by the investigator as not medically significant.

PRIOR CONCURRENT THERAPY:

• No limit to number of prior treatment regimens
• At least 30 days since prior therapy and recovered
• At least 3 months since prior autologous stem cell transplantation and recovered

• Prior allogeneic stem cell or bone marrow transplantation allowed provided the following criteria are met:

  • More than 1 year since transplantation
  • No longer receiving immunosuppressive therapy or treatment for graft-versus-host disease (GVHD) prophylaxis
  • No active GVHD
  • No active, uncontrolled infections
• No major surgery within the past 3 weeks
• No prior anthracycline dose > 360 mg/m^2 for doxorubicin hydrochloride (including pegylated liposomal doxorubicin hydrochloride [PLD]) or 720 mg/m^2 for epirubicin hydrochloride
• No prior or concurrent histone deacetylase inhibitor (e.g., valproic acid)
• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) during course 1
• No other concurrent investigational or anticancer agent