Liposomal Doxorubicin and Interleukin-12 in Treating Patients With AIDS-Related Kaposi's Sarcoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill the tumor cells. Combining chemotherapy with interleukin-12 may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining liposomal doxorubicin with interleukin-12 in treating patients who have AIDS-related Kaposi's sarcoma.

Detailed Description
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OBJECTIVES: Determine the overall response rate in patients with AIDS-associated Kaposi's sarcoma (KS) treated with doxorubicin HCl liposome and interleukin-12. Determine the time to response and the number of complete responses in patients treated with this regimen. Determine the progression-free survival of patients treated with this regimen. Provide pilot information on the ability of interleukin-12 to maintain major responses induced with paclitaxel salvage therapy in patients with aggressive or life-threatening KS after treatment failure with doxorubicin HCl liposome and interleukin-12. Determine the effect of this regimen on CD4 counts and viral load in these patients. OUTLINE: Patients receive doxorubicin HCl liposome (LipoDox) IV over 30 minutes once every 3 weeks for a total of 6 doses. Beginning concurrently with the initiation of LipoDox, patients also receive interleukin-12 (IL-12) subcutaneously twice weekly (at least 3 days apart) for up to 3 years. Patients with refractory disease are transferred to the paclitaxel salvage therapy regimen comprising paclitaxel IV continuously on days 1-4 once every 3 weeks until a major response is achieved. Beginning concurrently with the initiation of paclitaxel salvage therapy, patients also receive IL-12 as above for up to 3 years. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response may discontinue IL-12 administration. If necessary, IL-12 treatment may resume at a later time. Patients are followed at 4 weeks. PROJECTED ACCRUAL: A total of 24-36 patients will be accrued for this study within 2-4 years.

Official Title
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A Phase II Study of Liposomal Doxorubicin and Interleukin-12 in AIDS-Associated Kaposi's Sarcoma Followed by Chronic Administration of Interleukin-12

Conditions
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Sarcoma

Intervention / Treatment
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* Biological: recombinant interleukin-12
* Drug: paclitaxel
* Drug: pegylated liposomal doxorubicin hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed Kaposi's sarcoma (KS) HIV positive Evaluable disease involving the skin and/or viscera At least 5 lesions not previously treated with local therapy if restricted to the skin Pulmonary lesions evaluable by CT scan Gastrointestinal lesions evaluable by visualization or fiberoptic instrumentation Presence of at least one of the following indications for cytotoxic chemotherapy: Pulmonary involvement Visceral involvement Pain Edema Ulcerating lesions Decreased range of joint motion due to KS Multiple lesions not amenable to local therapy Lymphedema that impairs mobility or range of motion Significant psychological impact leading to social withdrawal Progressive disease within the past 3 weeks while receiving a stable regimen of highly active antiretroviral therapy for at least 4 weeks unless there is a need for urgent chemotherapy Prior participation on this study allowed, provided patient was removed from study due to non-pancreatic hyperamylasemia and the following are true: No dose-limiting toxicity by clinical and laboratory assessment Pancreatic amylase portion normal by fractionated amylase Lipase normal No symptoms referable to the pancreas PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 30-100% Life expectancy: More than 2 months Hematopoietic: Hemoglobin at least 9.0 g/dL Absolute neutrophil count at least 750/mm^3 Platelet count at least 75,000/mm^3 Hepatic: Bilirubin no greater than 3.8 mg/dL with direct fraction no greater than 0.3 mg/dL and indirect fraction no greater than 3.5 mg/dL if due to protease inhibitor therapy PT or aPTT no greater than 120% of control unless due to lupus-type anticoagulant AST no greater than 2.5 times upper limit of normal No prior hepatic cirrhosis No hepatic dysfunction Renal: Creatinine no greater than 1.5 mg/dL Creatinine clearance at least 60 mL/min Cardiovascular: No congestive heart failure Ejection fraction at least 40% by MUGA or echocardiogram Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for 2 months after study participation No clinically significant autoimmune disease No active, gross gastrointestinal bleeding or uncontrolled peptic ulcer disease No prior inflammatory bowel disease No other prior or concurrent malignancy except squamous cell carcinoma in situ of the cervix or anus, completely resected basal cell carcinoma, or malignancy in complete remission for at least 1 year from the time a response was first documented No severe or life-threatening infection within the past 2 weeks No abnormality that would be scored as grade 3 toxicity except lymphopenia or direct manifestations of KS No known hypersensitivity to interleukin-12 (IL-12) or other compounds known to cross-react with IL-12 No other medical condition that would preclude study entry PRIOR CONCURRENT THERAPY: Biologic therapy: More than 2 weeks since prior cytokines or colony-stimulating factors other than epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF) No prior combination interleukin-12 and doxorubicin HCl liposome except for patients previously treated on this protocol who are being enrolled for paclitaxel salvage therapy No concurrent immunomodulatory agents No concurrent cytokines except epoetin alfa or G-CSF Chemotherapy: See Disease Characteristics See Biologic therapy At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) More 6 months since prior suramin No other concurrent cytotoxic chemotherapy Endocrine therapy: More than 2 months since prior systemic glucocorticoid steroids at doses sufficient to affect immune response (e.g., more than 20 mg of prednisone for more than 1 week) Concurrent replacement glucocorticoid therapy allowed No other concurrent systemic glucocorticoid therapy Radiotherapy: Not specified Surgery: Not specified Other: Concurrent antiretroviral therapy required No other concurrent anti-KS therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: recombinant interleukin-12|nan|
|Drug: paclitaxel|nan|
|Drug: pegylated liposomal doxorubicin hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AIDS-related Kaposi sarcoma, recurrent Kaposi sarcoma