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

NCT01057121 | Completed Phase 1 Results DMC

• 4 other identifiers: NCI-2012-02923CDR0000664131AMC-070U01CA121947
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 13

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.

Conditions

AIDS-Related Kaposi Sarcoma; Recurrent Kaposi Sarcoma

Keywords

HIV Infections

Outcome Measures

Primary Outcomes (2)

• 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)

  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.

  28 days

• Tumor Response Rate

  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.

  Up to 30 days after completion of study treatment

Secondary Outcomes (3)

• 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

Other Outcomes (1)

• Relationship Between Clinical Response and Quantitative Measures of Kaposi's Sarcoma-associated Herpesvirus (KSHV)/HHV-8 and HIV Viral Load

  Up to 30 days after completion of study treatment

Study Arms (1)

Lenalidomide

EXPERIMENTAL

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.

Drug: Lenalidomide

Interventions

Lenalidomide DRUG

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

Also known as: Revlimid

Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (13)

UCLA Center for Clinical AIDS Research and Education

Los Angeles, California, 90035, United States

Location

University of California San Diego

San Diego, California, 92103, United States

Location

San Francisco General Hospital

San Francisco, California, 94110, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Cancer Center of Hawaii-Hawaii AIDS Clinical Research Program

Honolulu, Hawaii, 96816, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital

Baltimore, Maryland, 21231, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Pennsylvania Oncology Hematology Associates

Philadelphia, Pennsylvania, 19106, United States

Location

Thomas Street Clinic

Houston, Texas, 77009, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• Reid EG, Shimabukuro K, Moore P, Ambinder RF, Bui JD, Han S, Martinez-Maza O, Dittmer DP, Aboulafia D, Chiao EY, Maurer T, Baiocchi R, Mitsuyasu R, Wachsman W; AIDS Malignancy Consortium (AMC). AMC-070: Lenalidomide Is Safe and Effective in HIV-Associated Kaposi Sarcoma. Clin Cancer Res. 2022 Jun 13;28(12):2646-2656. doi: 10.1158/1078-0432.CCR-21-0645.

  PMID: 35247913 DERIVED

MeSH Terms

Conditions

AIDS-related Kaposi sarcoma; Sarcoma, Kaposi; HIV Infections

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: AMC Statistical Center
• Organization: AIDS Malignancy Consortium

jylee@uams.edu

501-526-6712

Study Officials

• Kelly Shimabukuro

  AIDS Associated Malignancies Clinical Trials Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2010
• First Posted: January 27, 2010
• Study Start: August 27, 2010
• Primary Completion: August 4, 2014
• Study Completion: August 4, 2014
• Last Updated: February 8, 2022
• Results First Posted: July 21, 2016

Record last verified: 2022-01

Locations

US (13)