Clinical Trial: Lenalidomide in Treating Patients With AIDS-Associated Kaposi's Sarcoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I/II Study of Lenalidomide in Patients With AIDS-Associated Kaposi's Sarcoma

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 Summary:

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]alp
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

• 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.
• 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.

Original Primary Outcome:

• Maximum tolerated dose of lenalidomide (phase I)
• Overall clinical response (phase II)

Current Secondary Outcome:

• Time to Death [ Time Frame: Up to 30 days after completion of study treatment ]
  Percentage of patients who died
• Time to Relapse [ Time Frame: Up to 30 days after completion of study treatment ]
  Percentage of participants who relapsed
• Time to Response [ Time Frame: Up to 30 days after completion of study treatment ]

  time from enrollment to first response (complete or partial) as defined below: Complete response is defined as the absence of any detectable residual disease, including tumor-associated edema, persisting for at least 4 weeks.

  Partial response is 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 lasting 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.

Original Secondary Outcome:

• Effects of lenalidomide on HIV plasma viral loads
• Effects of lenalidomide on T-lymphocyte subsets and NK cells
• Time to response, time to relapse, and time to death
• Effects of lenalidomide on HHV-8 copy number
• Relationship between HHV-8 gene expression and clinical response
• Effects of lenalidomide on growth factors relevant to tumor proliferation
• Effects of lenalidomide on viral and cellular genes
• Changes in NK cell number and function pre- and post-lenalidomide
• Sensitivity and specificity of dermal adhesive strip samples in detecting Kaposi sarcoma and the effects of lenalidomide on the lesions

Dates:
Date Received: January 26, 2010
Date Started: August 2010
Date Completion:
Last Updated: June 7, 2016
Last Verified: June 2016