Doxorubicin Hydrochloride Liposome and Bortezomib in Treating Patients With Refractory Hematologic Cancer or Malignant Solid Tumor or Metastatic Breast Cancer

DISEASE CHARACTERISTICS:

Phase I (closed to accrual as of 10/15/2007)

* Histologically or cytologically confirmed solid tumor or hematologic malignancy, including, but not limited to, any of the following:

  * Breast cancer
  * Ovarian cancer
  * Myeloid or lymphoid leukemia
  * Hodgkin or non-Hodgkin lymphoma
  * Multiple myeloma
* Measurable or evaluable disease
* Must meet 1 of the following criteria:

  * Refractory to at least one prior conventional treatment regimen
  * Not a candidate for conventional therapy
  * No conventional therapy exists
* No clinically or radiographically significant pleural or pericardial effusion

  * Patients with ascites may be eligible at the discretion of the investigator
* Previously treated central nervous system disease allowed provided it has been stable for \> 3 months and it is not the only site of measurable disease
* Not eligible for a higher priority protocol

Phase II

* Diagnosis of breast cancer

  * Metastatic disease
* Measurable disease by RECIST criteria
* No symptomatic brain metastases

  * Patients with treated brain metastases that have been stable for \> 3 months and does not require chronic steroids are eligible
* Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Phase I (closed to accrual as of 10/15/2007)

* Karnofsky performance status 60-100%
* Life expectancy ≥ 2 months
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* WBC ≥ 2,000/mm³
* ANC ≥ 1,500/mm³ (≥ 1,000/mm³ for patients with marrow infiltration)
* Platelet count ≥ 100,000/mm³ (≥ 50,000/mm³ for patients with marrow infiltration)
* Hemoglobin ≥ 8 g/dL
* Creatinine ≤ 2.5 mg/dL OR creatinine clearance ≥ 30 mL/min
* AST and ALT \< 2.5 times upper limit of normal (ULN)
* Total bilirubin \< 1.2 times ULN
* Prothrombin time (PT) and activated partial thromboplastin time (aPTT) \< 1.5 times ULN

  * Patients receiving warfarin or heparin therapy for a history of thrombosis, embolism, or other indication must have PT and/or aPTT within the accepted therapeutic ranges for those indications
* Patients with a history of reactions to other liposomal drug formulations that are not due to the liposome itself may be eligible at the discretion of the investigator
* No known HIV seropositivity
* No known active hepatitis A, B, or C viral infection
* No New York Heart Association class III or IV congestive heart failure
* LVEF ≥ 45% by 2-D ECHO or MUGA
* No acute ischemia or new conduction system abnormality by EKG
* No conduction system abnormality (e.g., left bundle branch block) by EKG that would preclude the ability to detect new ischemic episodes
* No myocardial infarction within the past 6 months
* No significant comorbidity, such as poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that, in the opinion of the investigator, might compromise any aspect of the study
* No uncontrolled infection

  * Patients may have febrile episodes up to 38.5°C if these are felt to be due to tumor fever and the possibility of infection has been ruled out by evaluation
* No prior hypersensitivity reaction to pegylated doxorubicin hydrochloride liposome or doxorubicin hydrochloride

  * Patients with a history of reactions to other liposomal drug formulations and/or to the liposome itself, as opposed to the encapsulated agent, may be excluded at the discretion of the investigator

Phase II

* Female or male
* Menopausal status not specified
* Karnofsky performance status 70-100%
* Life expectancy ≥ 3 months
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 3 months after completion of study therapy
* ANC ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 9.0 g/dL
* Creatinine ≤ 2.5 mg/dL (≤ 200 µmol/L)
* AST and ALT ≤ 2 times ULN
* Alkaline phosphatase ≤ 2 times ULN (unless attributed to tumor)
* Bilirubin ≤ ULN
* Cardiac ejection fraction \> 50% by MUGA or 2-D ECHO
* No clinical evidence of congestive heart failure
* No New York Heart Association class II-IV cardiac disease
* No myocardial infarction within the past 6 months
* No uncontrolled angina
* No severe uncontrolled ventricular arrhythmias
* No evidence of acute ischemia or active conduction system abnormalities by EKG

  * Any EKG abnormality at screening must be documented by the investigator as not medically relevant
* No grade 2 peripheral neuropathy within the past 14 days
* No significant comorbidity that would impair compliance with study therapy or interpretation of study results
* No history of hypersensitivity reactions attributed to a conventional formulation of doxorubicin hydrochloride or the components of pegylated doxorubicin hydrochloride liposome
* No hypersensitivity to bortezomib, boron, or mannitol
* No serious medical or psychiatric illness likely to interfere with participation in this study

PRIOR CONCURRENT THERAPY:

Phase I (closed to accrual as of 10/15/2007)

* More than 3 weeks since prior major surgery
* More than 3 weeks since prior and no concurrent radiotherapy
* More than 4 weeks since prior and no concurrent immunotherapy (i.e., interferon, interleukin, or other cytokine-based treatment)
* More than 3 weeks since prior and no concurrent participation in another therapeutic clinical trial with an experimental drug
* More than 3 weeks since prior and no other concurrent chemotherapy
* No prior doxorubicin dose \> 400 mg/m²
* No other concurrent antineoplastic therapy

Phase II

* More than 6 months since prior anthracyclines
* More than 14 days since other prior investigational drugs
* No more than 300 mg/m² of prior doxorubicin or 540 mg/m² of prior epirubicin
* No more than two prior chemotherapy regimens for metastatic disease
* No other concurrent antineoplastic therapy