Background: Kaposi sarcoma (KS) is a cancer that causes abnormal tissue to grow in the skin, lymph nodes, and other organs. KS is caused by a virus known as Kaposi sarcoma herpesvirus. People infected with human immunodeficiency virus (HIV) account for 80% of KS cases in the United States. Having HIV can weaken the immune system and this can lead to KS. Weaker immune systems may be measured by low T cells (a type of immune cell). CYT107 is a human protein, made in a laboratory, that may help boost immunity, specifically by increasing T cells, in people with HIV-associated KS. Objective: To see if CYT107 can shrink KS tumors. Eligibility: People aged 18 years and older with HIV-associated KS. Design: Participants will be screened. They will have a physical exam with blood tests. Their skin lesions will be measured. They will have an x-ray of their lungs. Their ability to perform everyday tasks will be reviewed. A sample of lesion tissue (biopsy) may be collected from the skin. CYT107 is injected into the muscle of the arm, buttocks, or lower thigh once a week for up to 4 weeks. Participants will receive the shots at the clinic. Blood and other tests will be repeated at each visit. KS lesions will be measured and photographed on the 1st and 4th visits. Participants who improved after the first 4 weeks may have another 4-week treatment within a year. Follow-up visits will continue for 3 years.
Background: * Kaposi sarcoma (KS) is an angioproliferative tumor associated with KS-associated herpes virus (KSHV), also known as human herpesvirus 8 or (HHV-8) infection. * Human immunodeficiency virus (HIV) infection-related KS accounts for greater than 80% of KS in the United States. * Survival rates from HIV-related KS are poorer than classic KS, despite improving substantially with the introduction of antiretroviral therapy (ART). * KS oncogenesis is associated with loss of T-cell mediated control of KSHV, the viral cause of KS. * While treatment of persons with HIV (PWH) with ART can improve T-cell counts and immunity, their T-cell counts often do not return to normal and they are often left with residual immunodeficiency. * There are a group of patients who have well controlled HIV but continue to have low CD4 T-cell counts (\<=350 cells/mcL) who are termed immune non-responders . This group possess a high rate of KS persistence, and chemotherapy can often contribute to lymphopenia. * The cytokine interleukin-7 (IL-7) plays an important role in T-cell development and proliferation and regulates T-cell homeostasis throughout life. * IL-7 administration is very potent at producing new T cells such as na(SqrRoot) ve T cells and recent thymic emigrants. * Administration of short acting recombinant human IL-7 was well-tolerated and has resulted in a dose-dependent increase in peripheral T cells and broadening of T-cell receptor (TCR) diversity. Objective: -To assess the overall response rate (ORR) of CYT107 defined as the best response (complete response \[CR\], clinical complete response \[CRR\], partial response \[PR\]) within 24 weeks in the first course of treatment, using the modified AIDS Clinical Trial Group (ACTG) KS response criteria in immune non-response participants with HIV-associated KS who had prior systemic KS therapy or who are KS therapy naive Eligibility: * Age \>=18 years * Histologically confirmed diagnosis of KS in people with HIV. * All participants should have at least five (5) measurable cutaneous KS lesions. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) \<=3 * CD4 T cell count \<=350 cells/mcL * This is an open label, nonrandomized Phase II study assessing the safety and activity of CYT107 in participants with HIV-associated KS. * Participants will be enrolled in two cohorts based on prior exposure to KS therapy. * A safety run-in will be conducted for the first 12 participants with no more than three participants treated simultaneously. * Participants will receive CYT107 at 20 mcg/kg by intramuscular (IM) injections every week for up to 4 weeks/4 doses. * Participants who have an increase in CD4 T-cell count following administration of CYT107 and evidence of KS response per ACTG criteria but subsequently experience a decrease in CD4 T-cell count (\>=100 cells/mcL) with associated deterioration in KS, or have had prior systemic KS therapy and first course resulted in SD only, may be eligible to receive a second course of CYT107 administration (for up to 4 weeks/4 doses). -Up to 29 evaluable participants will be enrolled.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
55
CYT107 is administered by IM injections at 20 mcg/kg every week for up to 4 weeks/4 doses
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Clinical benefit
Percentage of participants with the best overall response of CR, CRR, or PR to therapy.
Time frame: Baseline/prior to treatment (week 1/cycle 1), at cycle 4 (week 4), at EOT (week 8), at safety visits (weeks 12 and 16), and in follow-up (week 24 )
Safety of CYT107
Adverse events (AEs) will be reported by type and grade of toxicity
Time frame: Prior to each cycle, at EOT (week 8), and at safety visits (weeks 12 and 16)
Time of duration of response
The interval between initiating therapy and the time to disease progression in patients who achieve CR, PR, or SD.
Time frame: Baseline/prior to treatment (week 1/cycle 1), at cycle 4 (week 4), at EOT (week 8), at safety visits (weeks 12 and 16), and in follow-up (up to 3 years post-treatment)
Time of progression free survival
The interval between initiating therapy and the time to disease progression or death, whichever happens first
Time frame: Baseline/prior to treatment (week 1/cycle 1), at cycle 4 (week 4), at EOT (week 8), at safety visits (weeks 12 and 16), and in follow-up (up to 3 years post-treatment)
Proportion of participants requiring a second course of CYT107.
Percentage of participants who meet criteria and receive second course of treatment
Time frame: ongoing
Clinical benefit of a second course of CYT107
Percentage of participants that received a second course with the best overall response of CR, CRR, or PR to therapy.
Time frame: Baseline/prior to treatment (week 1/cycle 1), at cycle 4 (week 4), at EOT (week 8), at safety visits (weeks 12 and 16), and in follow-up (week 24 )
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