This study is NOT currently recruiting participants.
Number
000612-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: No longer recruiting/follow-up only Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Fetuses;Pregnant Women;Children
Keywords
AIDS; KSHV; Angiogenesis; Cytokine; CD4
Recruitment Keyword(s)
None
Condition(s)
Kaposi Sarcoma
Investigational Drug(s)
NT-I7 (rhIL-7-hyFc)
Investigational Device(s)
Intervention(s)
Drug: NT-I7
Supporting Site
National Cancer Institute
Kaposi sarcoma (KS) is a type of cancer. More than 80% of KS cases in the United States occur in people with human immunodeficiency virus (HIV) infection. KS can also occur among individuals without HIV. Researchers want to see if a drug called NT-I7 can help a person s immune system fight KS safely and without too many side effects.
Objective:
To learn the safety and potential side effects of drug NT-I7 in people who have KS with or without HIV.
Eligibility:
Adults aged 18 or older with a confirmed diagnosis of KS.
Design:
Participants will be screened with a physical exam and medical history. They will have blood and urine tests and a chest x-ray. They will have an electrocardiogram to record their heart s electrical activity. KS tumors will be measured. A pregnancy test, where applicable, will be required.
Some screening tests will be repeated during the study.
Participants will get a total of 4 doses of NT-I7. It will be injected into the muscle every 9 weeks for up to 27 weeks. They will be monitored for side effects after each dose, 30 days after the last dose, and then every 3 months until the study ends. Some participants may be able to continue the study treatment beyond the initial 4 doses.
Participants will have 2-3 tumor biopsies for research. Blood samples will also be taken for research.
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INCLUSION CRITERIA: - Patients must have histologically confirmed Kaposi sarcoma. - Patients must have evaluable disease. Note: Kaposi sarcoma will be evaluated using a modified version (consistent with NCI studies) of the AIDS Clinical Trial Group (ACTG) Oncology Committee staging and response definitions for KS. - No upper or lower limit on the number of prior therapies or stage of disease. No prior systemic therapy (other than ART for HIV) or local therapy is required. - HIV-positive patients must have been on effective anti-retroviral (ART) therapy for at least 3 months prior to enrollment, with persistent KS affecting quality of life due to either T(1) disease or T(0) disease with inadequate disease regression on ART alone. - HIV-positive patients must have undetectable HIV viral loads <=40 copies/mL measured using an FDA-approved commercial assay with lower limit of detection between <=20 copies/mL and <= 40 copies/mL. - Patients with visceral involvement must: -- Meet other eligibility criteria -- Have any/all associated tumor associated symptoms <= Grade 2 by CTCAE criteria; and/or -- Require no immediate intervention (e.g. mild oozing of oral KS not an exclusion criteria) - Patients must provide newly obtained core, punch, or excisional biopsy of a tumor lesion obtained up to 28 days prior to treatment initiation. An archival tumor sample obtained within 1 year of screening is allowed if pre-treatment biopsy is deemed unsafe or technically not feasible. - Patients must be >=18 years of age on day of signing informed consent document. Because no dosing or adverse event data are currently available on the use of NT-I7 in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric trials. - ECOG performance status 2 <= (Karnofsky >=60%). - Patients must have adequate organ and marrow function as defined below: -- leukocytes >=2,500/mcL -- absolute neutrophil count >=1,000/mcL -- platelets >=100,000/mcL -- hemoglobin >=9/dL -- total bilirubin <= 1.5 institutional upper limit of normal (ULN) OR <3 x institutional ULN for Gilbert s syndrome or HIV protease inhibitors AST(SGOT)/ALT(SGPT) <=2.5 x institutional ULN creatinine <= 2 x institutional ULN OR creatinine clearance <=60 mL/min/1.73 m2 by Cockroft-Gault: (140 - age) x (weight in kg) x (0.85 if female)/72 x (serum creatinine in mg/dL) At the discretion of the treating physician, a 24-hour urine creatinine clearance could be obtained and utilized as the gold standard if creatinine clearance by Cockcroft-Gault is <30 and prevents patient enrollment on the trial. - Patients with chronic hepatitis B virus (HBV) infection must be on suppressive antiviral therapy. - Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load due to prior treatment or natural resolution. - Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours before receiving the first dose of the study agent. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. - The effects of NT-I7 on the developing human fetus are unknown. For this reason and because NT-I7 may have an adverse effect on pregnancy and poses risk to the human fetus, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 90 days after completion of NT-I7 administration. - Ability to understand and the willingness to sign a written informed consent document. - Patients with impaired decision-making capacity will not be excluded. EXCLUSION CRITERIA: - Patients who have had chemotherapy, radiotherapy or other KS directed therapy other than ART for HIV within 2 weeks before the initiation of study treatment. - Patients who have not recovered from immune related adverse events due to prior therapy (i.e., have residual toxicities > Grade 1) with the exception of hypothyroidism managed by supplemental levothyroxine. - Patients who have received treatment with any other investigational agent within 4 weeks before initiation of study treatment. - Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies. - Patients who have a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. - Patients who have received treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2, pomalidomide, or immune checkpoint inhibitors) within 6 weeks before initiation of study treatment. - Patients who have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor [anti-TNF] agents) within 2 weeks before initiation of study treatment. - Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled. - The use of inhaled corticosteroids, and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed. - Patients who have a history or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener s granulomatosis, Sjogren s syndrome, Bell s palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis. Note: the following will NOT be exclusionary: -- The presence of laboratory evidence of autoimmune disease (e.g., positive antinuclear antibody (ANA) titer or lupus anticoagulant) without associated symptoms -- Clinical evidence of vitiligo or other forms of depigmenting illness -- Mild autoimmunity not impacting the function of major organs (e.g., limited psoriasis) - Patients with uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association Class III or IV), unstable angina pectoris, cardiac arrhythmia, recent myocardial infarction (within the last 6 months). Patients with known history of treatment with cardiotoxic agents, including anthracyclines, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. - Psychiatric illness/social situations that would limit compliance with study requirements. - Pregnant women are excluded from this study because the effects of NT-I7 on the developing human fetus are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with NT-I7, breastfeeding should be discontinued if the mother is treated with NT-I7. - Patients with a history of solid organ or allogeneic stem cell transplant. - Patients with continuing KS regression on ART alone. Stable disease allowed. - Patients with a prior or concurrent malignancy requiring active therapy. - Patients with active tuberculosis. - Patients who have a history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Patients must have histologically confirmed Kaposi sarcoma.
- Patients must have evaluable disease.
Note: Kaposi sarcoma will be evaluated using a modified version (consistent with NCI studies) of the AIDS Clinical Trial Group (ACTG) Oncology Committee staging and response definitions for KS.
- No upper or lower limit on the number of prior therapies or stage of disease. No prior systemic therapy (other than ART for HIV) or local therapy is required.
- HIV-positive patients must have been on effective anti-retroviral (ART) therapy for at least 3 months prior to enrollment, with persistent KS affecting quality of life due to either T(1) disease or T(0) disease with inadequate disease regression on ART alone.
- HIV-positive patients must have undetectable HIV viral loads <=40 copies/mL measured using an FDA-approved commercial assay with lower limit of detection between <=20 copies/mL and <= 40 copies/mL.
- Patients with visceral involvement must:
-- Meet other eligibility criteria
-- Have any/all associated tumor associated symptoms <= Grade 2 by CTCAE criteria; and/or
-- Require no immediate intervention (e.g. mild oozing of oral KS not an exclusion criteria)
- Patients must provide newly obtained core, punch, or excisional biopsy of a tumor lesion obtained up to 28 days prior to treatment initiation. An archival tumor sample obtained within 1 year of screening is allowed if pre-treatment biopsy is deemed unsafe or technically not feasible.
- Patients must be >=18 years of age on day of signing informed consent document. Because no dosing or adverse event data are currently available on the use of NT-I7 in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric trials.
- ECOG performance status 2 <= (Karnofsky >=60%).
- Patients must have adequate organ and marrow function as defined below:
-- leukocytes >=2,500/mcL
-- absolute neutrophil count >=1,000/mcL
-- platelets >=100,000/mcL
-- hemoglobin >=9/dL
-- total bilirubin <= 1.5 institutional upper limit of normal (ULN)
OR
<3 x institutional ULN for Gilbert s syndrome or HIV protease inhibitors
AST(SGOT)/ALT(SGPT) <=2.5 x institutional ULN
creatinine <= 2 x institutional ULN
creatinine clearance <=60 mL/min/1.73 m2 by Cockroft-Gault:
(140 - age) x (weight in kg) x (0.85 if female)/72 x (serum creatinine in mg/dL)
At the discretion of the treating physician, a 24-hour urine creatinine clearance could be obtained and utilized as the gold standard if creatinine clearance by Cockcroft-Gault is <30 and prevents patient enrollment on the trial.
- Patients with chronic hepatitis B virus (HBV) infection must be on suppressive antiviral therapy.
- Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load due to prior treatment or natural resolution.
- Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours before receiving the first dose of the study agent. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- The effects of NT-I7 on the developing human fetus are unknown. For this reason and because NT-I7 may have an adverse effect on pregnancy and poses risk to the human fetus, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 90 days after completion of NT-I7 administration.
- Ability to understand and the willingness to sign a written informed consent document.
- Patients with impaired decision-making capacity will not be excluded.
EXCLUSION CRITERIA:
- Patients who have had chemotherapy, radiotherapy or other KS directed therapy other than ART for HIV within 2 weeks before the initiation of study treatment.
- Patients who have not recovered from immune related adverse events due to prior therapy (i.e., have residual toxicities > Grade 1) with the exception of hypothyroidism managed by supplemental levothyroxine.
- Patients who have received treatment with any other investigational agent within 4 weeks before initiation of study treatment.
- Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies.
- Patients who have a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
- Patients who have received treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2, pomalidomide, or immune checkpoint inhibitors) within 6 weeks before initiation of study treatment.
- Patients who have received treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor [anti-TNF] agents) within 2 weeks before initiation of study treatment.
- Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled.
- The use of inhaled corticosteroids, and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
- Patients who have a history or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener s granulomatosis, Sjogren s syndrome, Bell s palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis.
Note: the following will NOT be exclusionary:
-- The presence of laboratory evidence of autoimmune disease (e.g., positive antinuclear antibody (ANA) titer or lupus anticoagulant) without associated symptoms
-- Clinical evidence of vitiligo or other forms of depigmenting illness
-- Mild autoimmunity not impacting the function of major organs (e.g., limited psoriasis)
- Patients with uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association Class III or IV), unstable angina pectoris, cardiac arrhythmia, recent myocardial infarction (within the last 6 months).
Patients with known history of treatment with cardiotoxic agents, including anthracyclines, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.
- Psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because the effects of NT-I7 on the developing human fetus are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with NT-I7, breastfeeding should be discontinued if the mother is treated with NT-I7.
- Patients with a history of solid organ or allogeneic stem cell transplant.
- Patients with continuing KS regression on ART alone. Stable disease allowed.
- Patients with a prior or concurrent malignancy requiring active therapy.
- Patients with active tuberculosis.
- Patients who have a history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
Principal Investigator
Referral Contact
For more information: