Biological Response Modifier Therapy. Interleukin-12, IL-12, NSC-672423.

Complete evaluation of KS lesions, including whole body counts and assessments will be performed every 4 weeks. Photographs and radiological studies will be performed every 8 weeks.

Condition	Treatment or Intervention	Phase
Acquired Immunodeficiency Syndrome Kaposi's Sarcoma HIV Infections	Drug: Interleukin-12	Phase I

Further Study Details: 

Expected Total Enrollment:  55

Kaposi's sarcoma (KS) is a neoplastic disorder that occurs with significantly increased frequency in the setting of infection with HIV. Although the exact pathogenesis of KS is unknown, there is substantial evidence that angiogenesis is central to the development of this disease. Interleukin-12 (IL-12) is a cytokine that has been shown to possess antitumor and immunomodulatory activity. In addition, it possesses potent antiangiogenic activity. We will administer IL-12 to up to 55 patients with AIDS-associated KS in a pilot/dose-escalating manner to assess the tolerability of IL-12 in this population as well as to obtain preliminary information regarding the anti-tumor activity, immunologic and virologic effects, as well as the angiogenic effects of IL-12 administered to patients with AIDS-associated KS.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Patients with HIV infection and biopsy confirmed Kaposi's sarcoma (KS) who have disease that is evaluable by non-invasive methods and a life expectancy of greater than 3 months.
All patients must also have serum antibodies to HIV as measured by ELISA and western blot.
Patients must be ambulatory with a Karnofsky performance status of greater than or equal to 70.
All patients must be receiving a stable dose of antiretroviral therapy consisting of but not limited to a combination of two or more of the following: AZT, ddI, ddC, 3TC, d4T, saquinavir, ritonavir, indinavir, a non-nucleoside reverse transcriptase inhibitor, or another protease inhibitor. Treatment with other agents is allowed as long as it is considered a community standard of care. The patients have to be on this regimen for 4 weeks prior to IL-12 therapy.
Patients must be greater than or equal to 18 years old and capable of giving informed consent.
All patients of child-fathering or -bearing potential must agree to use medically accepted birth control measures while on study and for 2 months afterward.
A total bilirubin less than or equal to 3.7 mg/dl with direct fraction less than or equal to 0.2 mg/dl and indirect fraction of less than or equal to 3.5 mg/dl in patients for whom these abnormalities are felt to be due to protease inhibitor therapy.
EXCLUSION CRITERIA:
Pregnancy, or the possibility of becoming pregnant during drug administration. All female patients of child-bearing potential must have a negative pregnancy test within 2 weeks of entry onto the study. All patients of child-fathering or -bearing potiential must agree to use medically accepted birth control measures while on study and for 2 months afterward. In addition, lactating/breast-feeding patients will not be allowed on this study.
Patients should not have acutely life-threatening visceral or pulmonary KS that may be responsive to other therapies will be ineligible. In addition, patients with actively bleeding or critically located KS lesions may, if in the judgment of the Principal Investigator or Study Chairperson, these lesions pose an immediate risk to the patient, be ineligible. However, patients with pulmonary disease and minimal to no symptoms who do not require immediate cytotoxic chemotherapy will be eligible for the study.
Any one of the following hematologic abnormalities:
1. A Hb less than 9.0 gm/dl or transfusion within 1 month prior to entry;
2. An absolute neutrophil count (ANC) less than 750 cells/mm(3);
3. A platelet count less than 75,000 cells/mm(3);
4. APTT or PT greater than 120% of control.
A history of hepatic cirrhosis or present hepatic dysfunction with: AST/GOT greater than 2.5 times the upper limit of normal.
Serum creatinine greater than 1.5 mg/dL and an estimated or measured creatinine clearance less than 60 mL/min.
Clinically significant autoimmune disease (i.e. disease caused by production of antibodies and/or an immunologic response by the body against itself, such as systemic lupus erythematosis), and/or rheumatologic disease.
Active, gross gastrointestinal bleeding or uncontrolled peptic ulcer disease.
A history of inflammatory bowel disease.
Past or present history of malignant tumors other than KS, with the exception of patients who have been in complete remission for greater than or equal to 1 year from the discontinuation of their therapy, or have completely resected basal cell carcinoma or in situ squamous cell carcinoma of the cervix.
Evidence of a severe or life-threatening infection with bacterial, viral, fungal, protozoal, or parasitic pathogens within 2 weeks of entry onto the study. In general, patients must not have had a fever of greater than or equal to 39 degrees C or greater within the 10 days prior to entry onto the study, unless it is evident that this is not due to a severe underlying infection.
Patients with any other abnormality, except lymphopenia or direct manifestations of KS, that would be scored as a grade 3 toxicity.
Known hypersensitivity to IL-12 or other compounds that are known to cross-react with IL-12.
Patients should have not previously received IL-12. However, patients who were initially treated at the 100 ng/kg dose level and were withdrawn from the study for reasons other than toxicity may be re-entered and treated with 300 ng/kg of IL-12, providing they have been off IL-12 for at least 6 months and meet the eligibility criteria for entry onto the study except for having to be on a stable dose of antiretroviral therapy for 4 weeks. These patients and only these patients may be entered regardless of the amount of time they have received their current retroviral regimen. Also, treatment within the last 6 months with suramin; treatment within the last 3 weeks with any cytotoxic chemotherapeutic agent or regimen (6 weeks for mitomycin C or nitrosoureas), interferon, other systemic anti-KS therapy or regimen, radiation therapy, or local treatment (such as intralesional injections); treatment within the last 2 weeks with cytokines or bone marrow stimulating factors other than erythropoietin (Epo); treatment within the last 2 months with systemic glucocorticoid steroids at doses sufficient to affect the immune response. In general, this would mean an equivalent of more than 20 mg of prednisone for more than 1 week.
Replacement glucocorticoid therapy would be allowed. Androgen or mineralocorticoid therapy is discouraged but allowed.
Inability to give informed consent or unwillingness to refrain from uprotected sexual contact or other activities that might result in re-infection with HIV.
Any medical condition that, in the opinion of the Principal Investigator or Study Chairperson, would preclude inclusion of a patient onto this research study.

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States

Study ID Numbers:  960113; 96-C-0113
Record last reviewed:  May 25, 2004
Last Updated:  May 26, 2004
Record first received:  November 3, 1999
ClinicalTrials.gov Identifier:  NCT00001508
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08