Natural Killer Cells and Bortezomib to Treat Cancer

• INCLUSION CRITERIA:

  1. Diagnosed with histologically confirmed metastatic solid tumor - cancer of the lung (small cell or non small cell), prostate (adenocarcinoma), colorectum, kidney (renal cell carcinoma), pancreas (adenocarcinoma), or malignant melanoma, and disease confirmed to be metastatic and unresectable for which standard curative or beneficial treatments are no longer effective.

     OR

     Diagnosed with a hematological malignancy (multiple myeloma, chronic myelogenous leukemia [CML] or chronic lymphocytic leukemia [CLL] or small lymphocytic lymphoma [SLL]) and disease resistant or refractory to standard therapy and CLL/SLL patients are required to have failed prior treatment with at least one nucleoside analogue. Myeloma patients are required to have disease which has progressed following treatment with bortezomib.

  2. At least 4 weeks since any prior systemic therapy (excluding corticosteroid therapy) to treat the underlying malignancy (standard or investigational).
  3. At least 2 weeks since prior palliative radiotherapy.
  4. Ages greater than or equal to 18 years and less than or equal to 70 years.
  5. Evidence of progressive disease over a 3-month interval.
  6. RBC transfusion independent (solid tumor patients only).

EXCLUSION CRITERIA:

1. Disease not evaluable radiographically (applies to solid tumor patients only).
2. Disease involving greater than 25% of the liver radiographically (estimated based on review of liver lesions seen on CT scan).
3. History of an allogeneic hematopoietic stem cell transplant.
4. Brain metastases (with the exception of patients with a single brain metastasis less than 1cm treated with either sterotactic or gamma knife radiotherapy) due to poor prognosis and potential for neurological dysfunction that would confound evaluation of neurological and other adverse events).
5. Peripheral neuropathy of grade greater than 1, which would require reduction of bortezomib dose.
6. Acute diffuse infiltrative pulmonary disease.
7. Acute pericardial disease.
8. Life expectancy less than 3 months.
9. ECOG performance status 2, 3 or 4.
10. Uncontrolled concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, life threatening cardiac arrhythmia. Patients with symptoms of coronary artery disease, cardiac arrhythmias or an abnormal thallium stress test must be evaluated and cleared by cardiology prior to enrollment.
11. Ongoing or active infection
12. Contraindication for administration of pentostatin, bortezomib, and/or interleukin-2.
13. Allergy or hypersensitivity to bortezomib, boron or mannitol by history.
14. Concurrent use of corticosteroids.

15. For all tumor types:

    Marrow function characterized by

    -Absolute neutrophil count less than 1,500/mcL (must be present off growth factors)

    Organ function characterized by

    • Total bilirubin greater than 3 times upper limit of normal
    • AST (SGOT)/ALT (SGPT) greater than 4 times upper limit of normal
    • Creatinine clearance less than 50 cc/min based on a 24 hour urine collection
    • Left ventricular ejection fraction less than 40% by echocardiogram (ECHO)
    • Hypercalcemia greater than 2.5 mmol/L

    For all Hematologic malignancies:

    Marrow function characterized by

    • Neutrophil count less than or equal to 500/mcl
    • Platelets less than or equal to 20,000/mcl
16. HIV-positive patients
17. Hepatitis C positive patients (Hep C PCR positive)
18. Active Hepatitis B infection (Hep B surface antigen positive)
19. Pregnant or nursing
20. Psychiatric illness/social situations that would limit compliance with study requirements and ability to comprehend the investigational nature of the study and provide informed consent.