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Pomalidomide in Treating Patients With Kaposi Sarcoma and Human Immunodeficiency Virus Infection

Primary Purpose

Human Immunodeficiency Virus 1 Positive, Skin Kaposi Sarcoma

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Laboratory Biomarker Analysis
Pomalidomide
Sponsored by
AIDS Malignancy Consortium
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Human Immunodeficiency Virus 1 Positive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Participants must have measurable cutaneous KS that has been pathologically confirmed by an acquired immunodeficiency syndrome (AIDS) Malignancy Consortium (AMC)-approved pathologist; diagnostic tissue must be available to satisfy the tissue submission requirements for central pathology review
  • Participants may not show evidence for ongoing improvement in KS lesions in the 4 weeks prior to enrollment
  • HIV positive. Documentation of HIV-1 infection by means of any one of the following:
  • HIV-1 RNA detection by a licensed HIV-1 RNA assay demonstrating >1000 RNA copies/mL confirmed by a licensed screening antibody and/or HIV antibody antigen combination assay;
  • Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or HIV rapid multispot antibody differentiation assay. NOTE: The term "licensed" refers to a kit that has been certified or licensed by an oversight body within the participating country and validated internally. WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky performance status [KPS] >= 50)
  • Life expectancy >= 12 weeks
  • Hemoglobin >= 8 g/dL
  • Absolute neutrophil count (ANC): >= 1,000 cells/mm^3 (1.0 x 10^9/L)
  • Platelets: >= 75,000 cells/mm^3 (75.0 x 10^9/L)
  • Total bilirubin: =< 1.5 times the upper limit of normal (ULN), unless the participant is receiving an antiretroviral drug known to be associated with increased bilirubin, in which case the direct fraction should be =< 2 times the ULN
  • Serum aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) / alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 2.5 x ULN
  • Estimated or measured creatinine clearance > 60 mL/minute (1.00 mL/s) (serum creatinine =< 2.0 mg/dL / 176.8 umol/L)
  • Currently receiving local standard of care antiretroviral therapy (ART) for >= 12 weeks, with HIV viral load =< 400 copies/mL; participants are required to be on antiretroviral regimens that are in accordance with the current International AIDS Society guidelines concurrently with chemotherapy; the specific agents are at the discretion of the investigator and the use of investigational agents currently available on an expanded access basis is allowed
  • A female of childbearing potential (FCBP) is a female who has achieved menarche at some point and who meets one of the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy, or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months), or 3) does not have a serum or plasma follicle stimulating hormone (FSH) > 40 mIU/mL and a history of amenorrhea x >= 1 year

    • 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 of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, including one of the following highly effective, long-acting methods, DepoProvera, an intrauterine device (IUD), an implant*, or bilateral tubal ligation, if it can be verified that the procedure was performed, and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide; FCBP must also agree to ongoing pregnancy testing
    • NOTE: Implants containing levonorgestrel and etonogestrel are prohibited in women receiving efavirenz, as drug interactions will render the implants ineffective
    • Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy
    • All participants must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure; serum or urine pregnancy testing will be repeated in FCBP, and must be negative, within 24 hours of starting each new cycle of pomalidomide
  • Able to take aspirin (>= 81 mg) daily as prophylactic anticoagulation
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Participants who are receiving any other investigational agents
  • Any prior use of thalidomide, lenalidomide, or pomalidomide
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to pomalidomide
  • Visceral disease requiring cytotoxic chemotherapy (i.e., pulmonary KS, symptomatic gastrointestinal KS). KS-related lymphedema is permitted.
  • Use of agents containing zidovudine (including Combivir and Trizivir) are prohibited; in order to be eligible, participants taking zidovudine must change to a different regimen at least 7 days prior to therapy initiation; changes to antiretroviral therapy (ART) therapy during the study may be made if medically necessary (toxicity, failure of regimen, etc.)

    • Use of medications or substances that are strong inhibitors of CYP1A2, which include amiodarone, cimetidine, fluoroquinolones (e.g., ciprofloxacin, enoxacin), fluvoxamine, and ticlopidine is prohibited
    • Use of erythropoietin is prohibited
    • Co-administration of corticosteroids greater than doses required for treatment of adrenal insufficiency is prohibited
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection for which the participant has not completed at least 14 days of therapy prior to study enrollment and/or is not clinically stable; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with pomalidomide
  • Specific KS therapy, including cytotoxic chemotherapy but not including ART, within the past 4 weeks
  • Use of other anticancer treatments or agents within the past 4 weeks
  • History of malignant tumors other than KS, unless:

    • In complete remission for >= 1 year, or
    • Completely resected basal cell carcinoma, or
    • In situ squamous cell carcinoma of the cervix or anus
  • Grade >= 1 peripheral neuropathy
  • History of myocardial infarction (MI), cerebrovascular accident, or venous or arterial thromboembolism, unless line-related thrombosis without embolus occurring within 1 year prior to study entry
  • Known procoagulant disorder including prothrombin gene mutation 20210, antithrombin III deficiency, protein C deficiency, protein S deficiency and antiphospholipid syndrome but not including heterozygosity for the factor V Leiden mutation or the presence of a lupus anticoagulant in the absence of other criteria for the antiphospholipid syndrome
  • Any condition, including the presence of current laboratory abnormalities or other factor that, in the opinion of the investigator, places the participant at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study

Sites / Locations

  • Moi University School of MedicineRecruiting
  • UNC Project MalawiRecruiting
  • Uganda Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (pomalidomide)

Arm Description

Patients receive pomalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Overall response rate
The binomial proportion and its 95% exact confidence interval will be used to estimate the overall response rate.
Complete response rate
The binomial proportion and its 95% exact confidence interval will be used to estimate the complete response rate
Incidence of adverse events defined as grade 3 or higher toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0
The binomial proportion and its 95% exact confidence interval will be used to estimate the proportion of participants who experience a grade 3 or higher toxicity.

Secondary Outcome Measures

Changes in CD4 T cell count
Changes in CD4 counts and human immunodeficiency virus (HIV) viral load will be evaluated using generalized estimating equations.
Changes in HIV viral load as measured by HIV quantitative polymerase chain reaction
Changes in CD4 counts and HIV viral load will be evaluated using generalized estimating equations.

Full Information

First Posted
July 18, 2018
Last Updated
July 13, 2023
Sponsor
AIDS Malignancy Consortium
Collaborators
National Cancer Institute (NCI), The Emmes Company, LLC, University of Arkansas, Montefiore Medical Center, University of Stellenbosch, Weill Medical College of Cornell University, University of California, Los Angeles
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1. Study Identification

Unique Protocol Identification Number
NCT03601806
Brief Title
Pomalidomide in Treating Patients With Kaposi Sarcoma and Human Immunodeficiency Virus Infection
Official Title
A Phase II Multicenter Study of Pomalidomide Monotherapy in HIV-Positive Individuals With Kaposi Sarcoma (KS) in Sub-Saharan Africa (SSA)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 26, 2021 (Actual)
Primary Completion Date
January 31, 2025 (Anticipated)
Study Completion Date
January 2, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AIDS Malignancy Consortium
Collaborators
National Cancer Institute (NCI), The Emmes Company, LLC, University of Arkansas, Montefiore Medical Center, University of Stellenbosch, Weill Medical College of Cornell University, University of California, Los Angeles

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II clinical trial studies the side effects of pomalidomide and how well it works in treating patients with Kaposi sarcoma and human immunodeficiency virus (HIV) infection. Biological therapies, such as pomalidomide, may stimulate the immune system in different ways and stop tumor cells from growing and it may also block the growth of new blood vessels necessary for tumor growth.
Detailed Description
PRIMARY OBJECTIVES: I. To determine if pomalidomide monotherapy induces a minimal level of antitumor efficacy to justify its further development for HIV-associated Kaposi sarcoma (KS) in sub-Saharan Africa and is safe and tolerable. SECONDARY OBJECTIVES: I. To evaluate the effects of pomalidomide monotherapy on standard measures of HIV control, i.e., CD4 counts and HIV viral loads, in this participant population. TERTIARY OBJECTIVES: I. To assess the effect of pomalidomide treatment on serum cytokine levels. II. To evaluate if changes in serum cytokine levels correlate with clinical response. OUTLINE: Patients receive pomalidomide orally (PO) once daily (QD) 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 every 12 weeks for 48 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Immunodeficiency Virus 1 Positive, Skin Kaposi Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (pomalidomide)
Arm Type
Experimental
Arm Description
Patients receive pomalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Pomalidomide
Other Intervention Name(s)
4-Amino thalidomide, Actimid, CC-4047, Imnovid, Pomalyst
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Overall response rate
Description
The binomial proportion and its 95% exact confidence interval will be used to estimate the overall response rate.
Time Frame
Up to 48 weeks
Title
Complete response rate
Description
The binomial proportion and its 95% exact confidence interval will be used to estimate the complete response rate
Time Frame
Up to 48 weeks
Title
Incidence of adverse events defined as grade 3 or higher toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0
Description
The binomial proportion and its 95% exact confidence interval will be used to estimate the proportion of participants who experience a grade 3 or higher toxicity.
Time Frame
Up to 30 days after the last dose of study treatment
Secondary Outcome Measure Information:
Title
Changes in CD4 T cell count
Description
Changes in CD4 counts and human immunodeficiency virus (HIV) viral load will be evaluated using generalized estimating equations.
Time Frame
Baseline to up to 30 days after last dose of study drug
Title
Changes in HIV viral load as measured by HIV quantitative polymerase chain reaction
Description
Changes in CD4 counts and HIV viral load will be evaluated using generalized estimating equations.
Time Frame
Baseline to up to 30 days after last dose of study drug
Other Pre-specified Outcome Measures:
Title
Changes in serum cytokine levels as measured by Luminex assay
Description
General estimating equations will be used to evaluate changes in cytokine levels over time. Logistic regression analyses will be used to evaluate the association between cytokine levels and clinical response.
Time Frame
Baseline to up to 48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants must have measurable cutaneous KS that has been pathologically confirmed by an acquired immunodeficiency syndrome (AIDS) Malignancy Consortium (AMC)-approved pathologist; diagnostic tissue must be available to satisfy the tissue submission requirements for central pathology review Participants may not show evidence for ongoing improvement in KS lesions in the 4 weeks prior to enrollment HIV positive. Documentation of HIV-1 infection by means of any one of the following: HIV-1 RNA detection by a licensed HIV-1 RNA assay demonstrating >1000 RNA copies/mL confirmed by a licensed screening antibody and/or HIV antibody antigen combination assay; Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 Western blot confirmation or HIV rapid multispot antibody differentiation assay. NOTE: The term "licensed" refers to a kit that has been certified or licensed by an oversight body within the participating country and validated internally. WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load. Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky performance status [KPS] >= 50) Life expectancy >= 12 weeks Hemoglobin >= 8 g/dL Absolute neutrophil count (ANC): >= 1,000 cells/mm^3 (1.0 x 10^9/L) Platelets: >= 75,000 cells/mm^3 (75.0 x 10^9/L) Total bilirubin: =< 1.5 times the upper limit of normal (ULN), unless the participant is receiving an antiretroviral drug known to be associated with increased bilirubin, in which case the direct fraction should be =< 2 times the ULN Serum aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) / alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 2.5 x ULN Estimated or measured creatinine clearance > 60 mL/minute (1.00 mL/s) (serum creatinine =< 2.0 mg/dL / 176.8 umol/L) Currently receiving local standard of care antiretroviral therapy (ART) for >= 12 weeks, with HIV viral load =< 400 copies/mL; participants are required to be on antiretroviral regimens that are in accordance with the current International AIDS Society guidelines concurrently with chemotherapy; the specific agents are at the discretion of the investigator and the use of investigational agents currently available on an expanded access basis is allowed A female of childbearing potential (FCBP) is a female who has achieved menarche at some point and who meets one of the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy, or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months), or 3) does not have a serum or plasma follicle stimulating hormone (FSH) > 40 mIU/mL and a history of amenorrhea x >= 1 year 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 of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, including one of the following highly effective, long-acting methods, DepoProvera, an intrauterine device (IUD), an implant*, or bilateral tubal ligation, if it can be verified that the procedure was performed, and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide; FCBP must also agree to ongoing pregnancy testing NOTE: Implants containing levonorgestrel and etonogestrel are prohibited in women receiving efavirenz, as drug interactions will render the implants ineffective Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy All participants must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure; serum or urine pregnancy testing will be repeated in FCBP, and must be negative, within 24 hours of starting each new cycle of pomalidomide Able to take aspirin (>= 81 mg) daily as prophylactic anticoagulation Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Participants who are receiving any other investigational agents Any prior use of thalidomide, lenalidomide, or pomalidomide History of allergic reactions attributed to compounds of similar chemical or biologic composition to pomalidomide Visceral disease requiring cytotoxic chemotherapy (i.e., pulmonary KS, symptomatic gastrointestinal KS). KS-related lymphedema is permitted. Use of agents containing zidovudine (including Combivir and Trizivir) are prohibited; in order to be eligible, participants taking zidovudine must change to a different regimen at least 7 days prior to therapy initiation; changes to antiretroviral therapy (ART) therapy during the study may be made if medically necessary (toxicity, failure of regimen, etc.) Use of medications or substances that are strong inhibitors of CYP1A2, which include amiodarone, cimetidine, fluoroquinolones (e.g., ciprofloxacin, enoxacin), fluvoxamine, and ticlopidine is prohibited Use of erythropoietin is prohibited Co-administration of corticosteroids greater than doses required for treatment of adrenal insufficiency is prohibited Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection for which the participant has not completed at least 14 days of therapy prior to study enrollment and/or is not clinically stable; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with pomalidomide Specific KS therapy, including cytotoxic chemotherapy but not including ART, within the past 4 weeks Use of other anticancer treatments or agents within the past 4 weeks History of malignant tumors other than KS, unless: In complete remission for >= 1 year, or Completely resected basal cell carcinoma, or In situ squamous cell carcinoma of the cervix or anus Grade >= 1 peripheral neuropathy History of myocardial infarction (MI), cerebrovascular accident, or venous or arterial thromboembolism, unless line-related thrombosis without embolus occurring within 1 year prior to study entry Known procoagulant disorder including prothrombin gene mutation 20210, antithrombin III deficiency, protein C deficiency, protein S deficiency and antiphospholipid syndrome but not including heterozygosity for the factor V Leiden mutation or the presence of a lupus anticoagulant in the absence of other criteria for the antiphospholipid syndrome Any condition, including the presence of current laboratory abnormalities or other factor that, in the opinion of the investigator, places the participant at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan E. Krown, MD
Organizational Affiliation
AIDS Malignancy Consortium
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Samantha Vogt, MD, MPH
Organizational Affiliation
Johns Hopkins University
Official's Role
Study Chair
Facility Information:
Facility Name
Moi University School of Medicine
City
Eldoret
Country
Kenya
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Naftali Busakhala
Phone
254-722-496-933
Email
nbusakhala@yahoo.com
First Name & Middle Initial & Last Name & Degree
Naftali Busakhala, MBChB MMed
Facility Name
UNC Project Malawi
City
Lilongwe
Country
Malawi
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bongani Kaimila
Phone
2651755056
Email
bkaimila@unclilongwe.org
First Name & Middle Initial & Last Name & Degree
Lameck Chinula, MBBS, FCOG, MMED
Facility Name
Uganda Cancer Institute
City
Kampala
Country
Uganda
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Abrahams Omoding
Phone
256-772-555-865
Email
omo2009abra@yahoo.co.uk
First Name & Middle Initial & Last Name & Degree
Abrahams Omoding, MBChB MMED

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Pomalidomide in Treating Patients With Kaposi Sarcoma and Human Immunodeficiency Virus Infection

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