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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03601806
Recruitment Status : Not yet recruiting
First Posted : July 26, 2018
Last Update Posted : February 11, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
The Emmes Company, LLC
University of Arkansas
University of California, Los Angeles
Information provided by (Responsible Party):
AIDS Malignancy Consortium

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.

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus 1 Positive Skin Kaposi Sarcoma Other: Laboratory Biomarker Analysis Drug: Pomalidomide Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Multicenter Study of Pomalidomide Monotherapy in HIV-Positive Individuals With Kaposi Sarcoma (KS) in Sub-Saharan Africa (SSA)
Estimated Study Start Date : May 1, 2020
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : May 31, 2021


Arm Intervention/treatment
Experimental: Treatment (pomalidomide)
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.
Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Pomalidomide
Given PO
Other Names:
  • 4-Amino thalidomide
  • Actimid
  • CC-4047
  • Imnovid
  • Pomalyst




Primary Outcome Measures :
  1. Overall response rate [ Time Frame: Up to 48 weeks ]
    The binomial proportion and its 95% exact confidence interval will be used to estimate the overall response rate.

  2. Complete response rate [ Time Frame: Up to 48 weeks ]
    The binomial proportion and its 95% exact confidence interval will be used to estimate the complete response rate

  3. 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 [ Time Frame: Up to 30 days after the last dose of study treatment ]
    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 :
  1. Changes in CD4 T cell count [ Time Frame: Baseline to up to 30 days after last dose of study drug ]
    Changes in CD4 counts and human immunodeficiency virus (HIV) viral load will be evaluated using generalized estimating equations.

  2. Changes in HIV viral load as measured by HIV quantitative polymerase chain reaction [ Time Frame: Baseline to up to 30 days after last dose of study drug ]
    Changes in CD4 counts and HIV viral load will be evaluated using generalized estimating equations.


Other Outcome Measures:
  1. Changes in serum cytokine levels as measured by Luminex assay [ Time Frame: Baseline to up to 48 weeks ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 ribonucleic acid (RNA) viral load.

NOTE: The term "licensed" refers to a United States (U.S.) Food and Drug Administration (FDA)-approved kit or for sites located in countries other than the U.S., a kit that has been certified or licensed by an oversight body within that country and validated internally.

World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) 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 ribonucleic acid (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 >= 3 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03601806


Locations
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Kenya
Moi University School of Medicine
Eldoret, Kenya
Contact: Naftali Busakhala    254-722-496-933    nbusakhala@yahoo.com   
Principal Investigator: Naftali Busakhala, MBChB MMed         
Tanzania
Bugando Medical Centre
Mwanza, Tanzania
Contact: Nestory Masalu    255-783-0-00004    nmasalu2000@yahoo.com   
Principal Investigator: Nestory Masalu, MD MMed         
Uganda
Uganda Cancer Institute
Kampala, Uganda
Contact: Abrahams Omoding    256-772-555-865    omo2009abra@yahoo.co.uk   
Principal Investigator: Abrahams Omoding, MBChB MMED         
Zimbabwe
University of Zimbabwe Clinical Research Centre / Parirenyatwa Hospital
Harare, Zimbabwe
Contact: Margaret Borok-Williams    263-4-791631 ext 2272    mborok@mweb.co.zw   
Principal Investigator: Margaret Borok-Williams, MBChB         
Sponsors and Collaborators
AIDS Malignancy Consortium
National Cancer Institute (NCI)
The Emmes Company, LLC
University of Arkansas
University of California, Los Angeles
Investigators
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Study Chair: Susan E. Krown, MD AIDS Malignancy Consortium
Study Chair: Samantha Vogt, MD, MPH Johns Hopkins University

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Responsible Party: AIDS Malignancy Consortium
ClinicalTrials.gov Identifier: NCT03601806    
Other Study ID Numbers: AMC-100
NCI-2017-00390 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AMC-100
AMC-100 ( Other Identifier: AIDS Malignancy Consortium )
AMC-100 ( Other Identifier: CTEP )
UM1CA121947 ( U.S. NIH Grant/Contract )
First Posted: July 26, 2018    Key Record Dates
Last Update Posted: February 11, 2020
Last Verified: February 2020

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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
Additional relevant MeSH terms:
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Acquired Immunodeficiency Syndrome
HIV Infections
Sarcoma, Kaposi
Sarcoma
Immunologic Deficiency Syndromes
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Herpesviridae Infections
DNA Virus Infections
Neoplasms, Vascular Tissue
Thalidomide
Pomalidomide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances