Nelfinavir Mesylate and Bortezomib in Treating Patients With Relapsed or Progressive Advanced Hematologic Cancer

DISEASE CHARACTERISTICS:

• Diagnosed with advanced hematologic malignancies meeting the following criteria:

  • Multiple myeloma

    • Received ≥ 2 lines of prior chemotherapy (induction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant with or without maintenance therapy is considered one line of therapy)
  • Acute myeloid leukemia
  • Acute lymphoblastic leukemia
  • Diffuse large B-cell lymphoma
  • Hodgkin lymphoma
  • Mantle cell lymphoma

  • Mature T- and NK-cell neoplasms restricted to the following WHO-defined entities:

    • T-cell prolymphocytic leukemia
    • T-cell large granular lymphocytic leukemia
    • Aggressive NK-cell leukemia
    • Adult T-cell leukemia/lymphoma
    • Extranodal NK/T-cell lymphoma (nasal type)
    • Mycosis fungoides
    • Sézary syndrome
    • Primary CD30-positive T-cell lymphoproliferative disorders
    • Primary cutaneous anaplastic large cell lymphoma
    • Primary cutaneous gamma-delta T-cell lymphoma
    • Peripheral T-cell lymphoma (not otherwise specified)
    • Angioimmunoblastic T-cell lymphoma
    • Anaplastic large cell lymphoma (ALK-positive/ALK-negative)
  • Grade 3B follicular lymphoma
• Relapsed following or progressed during standard therapy

• Meeting the following criteria:

  • Standard intensive therapy is not feasible
  • Current disease state for which there is no standard effective therapy
  • Refused standard therapy where no curative option exists

• Measurable disease, defined as the following:

  • Myeloma: measurable serum monoclonal protein > 1 g/dL for IgG, or > 0.5 g/dL for IgA, IgM or IgD, or difference between involved and uninvolved free light chain levels in serum > 100 mg/L
  • Lymphoma: must have ≥ 1 lesion measurable by CT (longest diameter ≥ 15 mm)
  • Acute leukemia: ≥ 20% blasts in bone marrow or in peripheral blood (≥ 200/mL blasts in peripheral blood)
• No HIV-associated lymphoma

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 75,000/mm³ (if bone marrow impairment, ≥ 20,000/mm^3)
• Hemoglobin > 80 g/L (if considered to be caused by the underlying hematologic malignancy or bone marrow impairment, > 80 g/L after transfusion)
• Bilirubin ≤ 1.5 times upper limit of normal (ULN) (if suspected hemolysis, direct bilirubin ≤ 1.5 times ULN)
• ALT ≤ 2.5 times ULN
• Calculated creatinine clearance > 30 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 months after completion of study treatment
• Willing and capable to comply with an oral regimen
• Capable of understanding information given by the investigator on the trial
• Able to adhere and remain in geographic proximity to allow proper staging, treatment, and followup
• No other non-hematologic malignancy within the past 5 years, except adequately treated cervical carcinoma in situ or localized nonmelanoma skin cancer
• No known chronic hepatitis B or C infection or known HIV infection

• No serious underlying medical condition (at the judgment of the investigator) which would impair the ability of the patient to participate in the trial, including any of the following:

  • Active autoimmune disease
  • Uncontrolled diabetes
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric disorder
• No myocardial infarction within the past 6 months
• No polyneuropathy > grade 1 significantly interfering with activities of daily living or painful polyneuropathy
• No known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No more than 4 prior lines of chemotherapeutic regimens (induction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant with or without maintenance therapy is considered one line of therapy)
• More than 30 days since prior treatment in a clinical trial

• More than 30 days since prior and no concurrent chemotherapy or biologic agents

  • For patients with acute leukemia, hydroxyurea may be given up to 48 hours before first administration of the trial treatment, and low dose cytarabine (up to 20 mg/m^2) and mitoxantrone up to 20 mg up to 14 days before first dosing
• At least 1 week since prior and no concurrent CYP3A4 modulators
• No concurrent other experimental drugs
• No concurrent radiotherapy
• No concurrent antineoplastic therapy with chemotherapeutic or biologic agents