Lenalidomide in Treating Patients With AIDS-Associated Kaposi's Sarcoma
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.
AIDS-related Kaposi Sarcoma
Recurrent Kaposi Sarcoma
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Lenalidomide in Patients With AIDS-Associated Kaposi's Sarcoma|
- 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 ] [ Designated as safety issue: Yes ]Toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
- Tumor response rate [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]Estimated for each dose group and for all groups combined. The 95% confidence intervals will be constructed.
- Time to response [ Time Frame: From the first dose of chemotherapy until documentation of first response, assessed up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]Estimated using the Kaplan-Meier method.
- Time to relapse [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]Estimated using the Kaplan-Meier method.
- Time to death [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]Estimated using the Kaplan-Meier method.
- Relationship between clinical response and quantitative measures of Kaposi's sarcoma-associated herpesvirus (KSHV)/HHV-8 and HIV viral load [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]Spearman rank correlation analysis will be used to evaluate the relationship between the qualification of baseline KSHV/HHV-8, HIV viral load and time to progression, and response duration.
|Study Start Date:||August 2010|
|Estimated Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (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.
Other Names:Other: laboratory biomarker analysis
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)
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01057121
|United States, California|
|UCLA Center for Clinical AIDS Research and Education|
|Los Angeles, California, United States, 90035|
|University of California San Diego|
|San Diego, California, United States, 92103|
|San Francisco General Hospital|
|San Francisco, California, United States, 94110|
|United States, Florida|
|University of Miami Miller School of Medicine-Sylvester Cancer Center|
|Miami, Florida, United States, 33136|
|United States, Hawaii|
|Cancer Center of Hawaii-Hawaii AIDS Clinical Research Program|
|Honolulu, Hawaii, United States, 96816|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21231|
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|United States, Pennsylvania|
|Pennsylvania Oncology Hematology Associates|
|Philadelphia, Pennsylvania, United States, 19106|
|United States, Texas|
|Thomas Street Clinic|
|Houston, Texas, United States, 77009|
|United States, Washington|
|Harborview Medical Center|
|Seattle, Washington, United States, 98104|
|Virginia Mason Medical Center|
|Seattle, Washington, United States, 98101|
|Principal Investigator:||Kelly Shimabukuro||AIDS Associated Malignancies Clinical Trials Consortium|