Bortezomib, Doxorubicin Hydrochloride Liposome, and Rituximab in Treating Patients With Diffuse Large B-Cell Lymphoma That Has Relapsed or Not Responded to Treatment
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse
Intervention: rituximab; bortezomib; pegylated liposomal doxorubicin hydrochloride; gene expression analysis; polymerase chain reaction; polymorphism analysis; proteomic profiling; flow cytometry; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Given IV; Correlative Study; Correlative Study; Correlative Study; Correlative Study; Correlative Study; Correlative Study
Intervention MeSH terms: Rituximab; Doxorubicin; Liposomal doxorubicin; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; anaplastic large cell lymphoma

Summary:

      RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth and by blocking blood flow to the cancer. Drugs used in chemotherapy,
      such as doxorubicin hydrochloride liposome, work in different ways to stop the growth of
      cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal
      antibodies, such as rituximab, can block cancer cell growth in different ways. Some block the
      ability of cancer cells to grow and spread. Others find cancer cells and help kill them or
      carry cell-killing substances to them. Giving bortezomib together with doxorubicin
      hydrochloride liposome and rituximab may kill more cancer cells.

      PURPOSE: This phase II trial is studying how well giving bortezomib together with doxorubicin
      hydrochloride liposome and rituximab works in treating patients with diffuse large B-Cell
      lymphoma that has relapsed or not responded to treatment.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of CD20-positive diffuse large B-cell lymphoma, including any of the
             following morphological variants:

               -  Centroblastic

               -  Immunoblastic

               -  T-cell/histiocyte-rich

               -  Anaplastic

               -  Mediastinal (thymic) large B-cell lymphoma

               -  Intravascular large B-cell lymphoma

          -  Relapsed or refractory disease

          -  Measurable disease, defined as tumor size 2 cm²

          -  Must have received ≥ 1 prior standard chemotherapy regimen

          -  No Burkitt or precursor B-lymphoblastic lymphoma

          -  No brain involvement or evidence of CNS lymphoma

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance status (PS) 70-100% OR ECOG PS 0-2

          -  Life expectancy ≥ 12 weeks

          -  Absolute neutrophil count ≥ 1,500/μL*

          -  Platelet count ≥ 100,000/μL*

          -  Creatinine < 2.5 mg/dL OR > 40 mL/min*

          -  Hemoglobin > 8.0 g/dL*

          -  AST/ALT < 2 times upper limit of normal (ULN) (< 3 times ULN with liver involvement)*

          -  Alkaline phosphatase < 2 times ULN (< 3 times ULN with liver involvement)*

          -  Total bilirubin < 2 times ULN (< 3 times ULN with liver involvement or Gilbert
             disease)* NOTE: *Unless attributable to non-Hodgkin lymphoma

          -  LVEF ≥ 50% by MUGA scan or ECHO

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 6 months after
             completion of therapy

          -  No HIV positivity

          -  No hepatitis B positivity

          -  Peripheral neuropathy < grade 2 as defined by NCI CTCAE v 3.0

          -  No history of uncontrolled orthostatic hypotension

          -  None of the following cardiac conditions:

               -  Myocardial infarction within the past 6 months

               -  New York Heart Association class II-IV congestive heart failure

               -  Uncontrolled angina

               -  Severe uncontrolled ventricular arrhythmias

               -  Clinically significant pericardial disease

               -  ECG evidence of acute ischemic or active conduction system abnormalities

          -  No hypersensitivity to bortezomib, boron, or mannitol

          -  No history of allergic reactions to compounds containing boron, mannitol, bortezomib,
             conventional formulation of doxorubicin hydrochloride, or the components of pegylated
             liposomal doxorubicin hydrochloride

          -  No uncontrolled intercurrent illness including, but not limited to, any of the
             following:

               -  Ongoing or active infection

               -  Poorly controlled hypertension

               -  Diabetes mellitus

               -  Serious medical or psychiatric conditions that would interfere with adherence to
                  or completion of this study

          -  No other primary malignancy except squamous cell or basal cell carcinoma of the skin,
             in situ carcinoma of the cervix, superficial bladder carcinoma, or previously treated
             localized prostate cancer with normal PSA levels and disease-free for ≥ 5 years

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  Recovered from significant toxicity associated with prior surgery, radiotherapy,
             chemotherapy, or immunotherapy

          -  Prior rituximab or other monoclonal immunotherapy allowed

          -  More than 4 weeks since prior investigational drugs

          -  More than 4 weeks since prior chemotherapy

          -  More than 4 weeks since prior major surgery, other than diagnostic surgery

          -  No prior doxorubicin hydrochloride (or equivalent) anthracycline treatment exceeding
             400 mg/m²

          -  No concurrent corticosteroids, except to control a transient inflammatory reaction
             (i.e., skin rash or hives)

               -  Concurrent non-steroidal hormones administered for non-lymphoma related
                  conditions (e.g., insulin for diabetes) allowed

          -  No concurrent radiotherapy

          -  No other concurrent antitumor or chemotherapeutic agents

          -  No other concurrent investigational agents