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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
First received: January 26, 2010
Last updated: April 9, 2015
Last verified: April 2015
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.

Condition Intervention Phase
AIDS-Related Kaposi Sarcoma
Recurrent Kaposi Sarcoma
Other: Laboratory Biomarker Analysis
Drug: Lenalidomide
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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.

Secondary Outcome Measures:
  • 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.

  • 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 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.

Other Outcome Measures:
  • 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.

Enrollment: 32
Study Start Date: August 2010
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Laboratory Biomarker Analysis
Correlative studies
Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

Detailed Description:


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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  • Life expectancy >= 3 months
  • Ability and willingness to give informed consent
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours prior to starting Cycle 1 of lenalidomide; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide, during receipt of lenalidomide, and 28 days after discontinuation of lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • Patients must, in the opinion of the investigator, be capable of complying with the protocol
  • All patients must be on antiretroviral therapy for HIV infection with CD4 count > 50/mm^3 and viral load < 2,000 copies/mL; patients must be on a stable regimen for at least 12 weeks prior to study entry; patients may receive any FDA approved antiretroviral therapy except for zidovudine

    • There should be no evidence for improvement in KS in the 3 months prior to study entry, unless there is evidence for progression of KS in the 4 weeks immediately prior to study entry
    • If antiretroviral regimen contains zidovudine and viral load is suppressed (as measured by HIV viral load =< 200/mL), then antiretroviral therapy must be adjusted to a less toxic therapy not containing zidovudine and enrollment may proceed without waiting 12 weeks; if on zidovudine-containing therapy and viral load is not suppressed (as measured by HIV viral load >= 200/mL), then antiretroviral therapy must be adjusted to a less toxic regimen allowing for optimal viral suppression and must demonstrate stability for at least 12 weeks prior to study entry
  • Patients with any history of pulmonary embolism (PE) or deep venous thrombosis (DVT) or predisposing clotting risk factors must be on anticoagulation at therapeutic dosing

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
  • Previous local therapy of any KS-indicator lesion unless the lesion has clearly progressed since treatment; any prior local treatment to indicator lesions regardless of the elapsed time should not be allowed unless there is evidence of clear-cut progression of said lesion
  • Use of any investigational drug or treatment within 4 weeks prior to enrollment
  • Physical or psychiatric conditions that in the estimation of the investigator place the patient at high risk of toxicity or non-compliance
  • Female patients who are pregnant or breast-feeding
  • Patients with a history of DVT or PE within 1 year
  • Patients requiring blood transfusions to maintain Hgb eligibility
  • Patients on erythropoietin-stimulating agents (ESA) unless also on therapeutic anticoagulation
  • Patients with CD4 < 50 mm^3 and/or viral load > 2,000 copies/mL
  • Patients on estrogen therapy unless also on therapeutic anticoagulation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 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
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Kelly Shimabukuro AIDS Associated Malignancies Clinical Trials Consortium
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01057121     History of Changes
Other Study ID Numbers: NCI-2012-02923  NCI-2012-02923  CDR0000664131  AMC-070  AMC-070  U01CA121947 
Study First Received: January 26, 2010
Last Updated: April 9, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
HIV Infections

Additional relevant MeSH terms:
AIDS-Related Opportunistic Infections
Sarcoma, Kaposi
DNA Virus Infections
HIV Infections
Herpesviridae Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Vascular Tissue
Opportunistic Infections
Parasitic Diseases
RNA Virus Infections
Retroviridae Infections
Virus Diseases
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on May 26, 2016