A Phase I/II Study of Lenalidomide in Patients With AIDS-Associated Kaposi's Sarcoma
Overview
- Phase
- Phase 1
- Intervention
- Lenalidomide
- Conditions
- AIDS-Related Kaposi Sarcoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 38
- Locations
- 13
- Primary Endpoint
- Tumor Response Rate
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This phase I/II trial studies the side effects and best dose of lenalidomide and to see how well it works in treating patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (KS). Lenalidomide may stop the growth of tumor cells by blocking blood flow to the tumor.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of single agent lenalidomide in subjects with AIDS-related KS. (Phase I) II. Evaluate the overall clinical response of KS tumors to lenalidomide with subset assessments of partial response (PR) and complete response (CR). (Phase II) SECONDARY OBJECTIVES: I. Evaluate the effect of lenalidomide on human immunodeficiency virus (HIV) plasma viral loads. II. Determine the effects of lenalidomide on T-lymphocyte subsets, including natural killer (NK) cells. III. Evaluation of time to response, time to relapse, and time to death amongst subjects receiving lenalidomide. IV. Determine the effect of lenalidomide on human herpesvirus (HHV)-8. V. Assess lenalidomide effects on HHV-8 copy number in peripheral blood mononuclear cell (PBMC), and plasma and whether changes in viral copy number measured in PBMC or plasma are associated with clinical response of KS tumors. VI. Monitor HHV-8 gene expression in KS biopsy specimens and PBMC pre- and post-lenalidomide and assess whether changes in viral gene expression in tumor biopsy are associated with clinical response. VII. Assess whether changes in viral copy number in the compartments assayed occur in concert or independently with changes in viral antigen expression in biopsy specimens. VIII. Assess effects of lenalidomide on growth factors relevant to tumor proliferation (i.e., interleukin \[IL\]-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-15, IL-12p70, tumour necrosis factor \[TNF\]alpha, and interferon gamma \[IFN\]gamma). IX. Characterize the effects of lenalidomide on viral and cellular gene in KS tumor biopsies. X. Assess changes in NK cell number (PBMC and tumor) and function pre- and post-lenalidomide. XI. Assess the sensitivity and specificity of dermal adhesive strip samples to detect KS and the effects of lenalidomide on the lesions. OUTLINE: This is a multicenter study. This is a phase I, dose-escalation study of lenalidomide followed by a phase II study. Patients receive lenalidomide orally (PO) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Biopsy-proven KS involving skin with or without visceral involvement either newly diagnosed or refractory to or intolerant of one or more prior therapies
- •Patients must have cutaneous lesion(s) amenable to four 3 mm tumor biopsies during the study (either 4 separate lesions measuring \> 4 mm each OR 2 separate lesions measuring \> 8 mm each) and at least five additional lesions measurable for assessment with no improvement over the past month
- •Serologic documentation of HIV infection by any of the Food and Drug Administration (FDA)-approved tests
- •Karnofsky performance status \>= 60%
- •Hemoglobin \>= 8 g/dL
- •Absolute neutrophil count (ANC) \>= 1,000 cells/mm\^3
- •Platelet count \>= 100,000/mm\^3
- •Calculated (method of Cockcroft-Gault) creatinine clearance (CrCl) \>= 60 mL/min in the Phase I and CrCl \>= 30 mL/min in the Phase II (creatinine clearance may also be obtained by the 24-hour collection method at the investigator's discretion)
- •Total bilirubin should be =\< 1.5x upper limit of normal (ULN); if, however, the elevated bilirubin is felt to be secondary to Atazanavir therapy, patients will be allowed to enroll on protocol if the total bilirubin is =\< 3.5 mg/dL provided that the direct bilirubin is normal
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3x ULN
Exclusion Criteria
- •Concurrent, acute, active opportunistic infection other than oral thrush or genital herpes within 14 days of enrollment
- •Patients for whom front-line cytotoxic therapy is indicated (i.e. symptomatic visceral or pulmonary KS or symptomatic KS impairing functional status)
- •Concurrent neoplasia requiring cytotoxic therapy
- •Acute treatment for an infection (other than oral thrush or genital herpes) or other serious medical illness within 14 days of study entry
- •Anti-neoplastic treatment for KS (including chemotherapy, radiation therapy, local therapy including topical 5-FU, biological therapy, or investigational therapy) within four weeks of study entry
- •Any steroid treatment except for that required for replacement therapy in adrenal insufficiency or inhaled steroids for the treatment of asthma
- •Patient is =\< 2 years free of another primary malignancy; exceptions include the following:
- •Basal cell skin cancer
- •Cervical carcinoma in situ
- •Anal carcinoma in situ
Arms & Interventions
Lenalidomide
Patients receive lenalidomide PO once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Lenalidomide
Outcomes
Primary Outcomes
Tumor Response Rate
Time Frame: Up to 30 days after completion of study treatment
Percentage of patients who achieve a partial or complete response Complete response was defined as the absence of any detectable residual disease, including tumor-associated edema, that persisted for at least 4 weeks. Partial response was defined as no new lesions (skin or oral), or new visceral sites of involvement (or the appearance or worsening of tumor-associated edema or effusions), and a 50% or greater decrease in the number of all previously existing lesions that lasted for at least 4 weeks, or complete flattening of at least 50% of all previously raised lesions, or a 50% or greater decrease in the sum of the products of the largest perpendicular diameters of the marker lesions.
Maximum Tolerated Dose of Lenalidomide Defined as the Dose Level at Which 0/6 or 1/6 Subjects Experience Dose Limiting Toxicity (DLT) With the Next Higher Dose Having at Least 2/3 or 2/6 Subjects Encountering DLT (Phase I)
Time Frame: 28 days
Maximum tolerated dose (MTD) of lenalidomide defined as the dose level at which 0/6 or 1/6 subjects experience dose limiting toxicity (DLT) with the next higher dose having at least 2/3 or 2/6 subjects encountering DLT (Phase I). Toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Using a 3+3 design, the MTD is defined as the level at which 0/6 or 1/6 patients experiences at dose-limiting toxicity in the first cycle.
Secondary Outcomes
- Time to Death(Up to 30 days after completion of study treatment)
- Time to Relapse(Up to 30 days after completion of study treatment)
- Time to Response(Up to 30 days after completion of study treatment)