Lenalidomide in Treating Patients With AIDS-Associated Kaposi's Sarcoma
|ClinicalTrials.gov Identifier: NCT01057121|
Recruitment Status : Completed
First Posted : January 27, 2010
Results First Posted : July 21, 2016
Last Update Posted : July 21, 2016
|Condition or disease||Intervention/treatment||Phase|
|AIDS-Related Kaposi Sarcoma Recurrent Kaposi Sarcoma||Drug: Lenalidomide||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of Lenalidomide in Patients With AIDS-Associated Kaposi's Sarcoma|
|Study Start Date :||August 2010|
|Actual Primary Completion Date :||June 2014|
|Actual Study Completion Date :||June 2014|
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.
Lenalidomide is administered daily on days 1-21 of a 28-day cycle. The maximum duration of treatment is 12 28-day cycles. Sequential cohorts were entered at 10 mg/day, 15 mg/day, 20 mg/day and 25 mg/day using a 3+3 design to determine the MTD
Other Name: Revlimid
- 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.
- 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.
- 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 ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 Comprehensive Cancer 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|
|Virginia Mason Medical Center|
|Seattle, Washington, United States, 98101|
|Harborview Medical Center|
|Seattle, Washington, United States, 98104|
|Principal Investigator:||Kelly Shimabukuro||AIDS Associated Malignancies Clinical Trials Consortium|