- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04893018
NT-I7 for Kaposi Sarcoma in Patients With or Without HIV
Phase 1 Study of NT-I7 (rhIL-7-hyFc) for the Treatment of Kaposi Sarcoma in Patients With or Without Infection With HIV
Study Overview
Status
Intervention / Treatment
Detailed Description
OUTLINE: This is a dose-escalation study.
Patients receive efineptakin alfa intramuscularly (IM) on day 1. Cycles repeat every 9 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up on day 30 (+/- 7 days) and then every 12 weeks for 12 months.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: CITN Central Operations and Statistical Center Coordinator
- Phone Number: 206.667.5000
- Email: citn@fredhutch.org
Study Locations
-
-
California
-
San Francisco, California, United States, 94110
- Zuckerberg San Francisco General Hospital
-
-
Maryland
-
Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center
-
-
Washington
-
Seattle, Washington, United States, 98104
- Harborview Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 National Cancer Institute [NCI] studies) of the Acquired Immunodeficiency Syndrome (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
- 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 T1 disease or T0 disease with inadequate disease regression on ART alone
- HIV-positive patients must have undetectable HIV viral loads =< 40 copies/mL measured using a Food and Drug Administration (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 Common Terminology Criteria for Adverse Events (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
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- 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
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x institutional ULN
- Creatinine =< 2 x institutional ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 by Cockcroft-Gault. 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
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 X-Ray. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (efineptakin alfa)
Patients receive efineptakin alfa IM on day 1.
Cycles repeat every 9 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
|
Given IM
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events
Time Frame: Up to 30 days after last dose of NT-I7
|
Measured by Common Terminology Criteria for Adverse Events version 5.0.
|
Up to 30 days after last dose of NT-I7
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate (ORR)
Time Frame: 12 months
|
Will be assessed according to modified Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group Criteria (ACTG) criteria.
|
12 months
|
Duration of response (DOR)
Time Frame: Up to 1 year
|
Will be measured in subjects who obtain a partial response or better and defined as time from the best response within the first 36 weeks of therapy until disease progression or censoring.
Kaplan Meier survival estimates will be constructed for each of these survival endpoints with 95% confidence intervals (CIs), for up to 1 year following initiation of treatment in all participants.
|
Up to 1 year
|
Progression-free survival (PFS)
Time Frame: From the time from administration of the first dose of NT-I7 until disease progression or death or censoring, assessed up to 1 year
|
Kaplan Meier survival estimates will be constructed for each of these survival endpoints with 95% CIs, for up to 1 year following initiation of treatment in all participants.
|
From the time from administration of the first dose of NT-I7 until disease progression or death or censoring, assessed up to 1 year
|
Overall survival (OS)
Time Frame: From administration of the first dose of NT-I7 until death or censoring, assessed up to 1 year
|
Kaplan Meier survival estimates will be constructed for each of these survival endpoints with 95% CIs, for up to 1 year following initiation of treatment in all participants.
|
From administration of the first dose of NT-I7 until death or censoring, assessed up to 1 year
|
Kinetics of CD4+ and CD8+ T cells in blood, and on levels and phenotype within tumors
Time Frame: Up to 12 months after last dose of NT-I7
|
Up to 12 months after last dose of NT-I7
|
|
Immunogenicity of NT-I7
Time Frame: Up to 12 months after last dose of NT-I7
|
The proportion of participants developing neutralizing antibodies will be summarized.
|
Up to 12 months after last dose of NT-I7
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Chia-Ching (Jackie) Wang, University of California, San Francisco
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CITN-17
- UM1CA154967 (U.S. NIH Grant/Contract)
- NCI-2021-01002 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on HIV Infection
-
Erasmus Medical CenterNot yet recruitingHIV Infections | Hiv | HIV-1-infection | HIV I InfectionNetherlands
-
Sociedad Andaluza de Enfermedades InfecciosasConsejeria de Salud. Junta de Andalucia. SpainCompletedHIV Infection | HIV-1 InfectionSpain
-
Allegheny Singer Research Institute (also known...Active, not recruitingHIV Infections | HIV-1-infection | HIV I InfectionUnited States
-
Beckman Coulter, Inc.CompletedHIV I Infection | HIV-2 InfectionFrance
-
Rockefeller UniversityCompletedHIV Infection | Healthy Volunteers | HIV-1 InfectionUnited States
-
Erasmus Medical CenterRecruitingHIV Infections | HIV-1-infection | HIV-2 InfectionNetherlands
-
Erasmus Medical CenterActive, not recruitingHIV Infections | HIV-1-infection | HIV-2 InfectionNetherlands
-
AIDS Healthcare FoundationUniversity of California, Los AngelesCompleted
-
Merck Sharp & Dohme LLCCompleted
-
National Institute of Allergy and Infectious Diseases...CompletedHIV-1 Infection | HIV Antibodies | Neutralizing Antibody | Viral Load | Monoclonal AntibodyUnited States
Clinical Trials on Efineptakin alfa
-
NeoImmuneTechNational Institute of Allergy and Infectious Diseases (NIAID); University of...Terminated
-
PT Kalbe Genexine BiologicsGenexine, Inc.Recruiting
-
Genexine, Inc.Terminated
-
Hyunseok Kang, MDNeoImmuneTechRecruitingRecurrent Head and Neck Squamous Cell Carcinoma | Recurrent Hypopharyngeal Squamous Cell Carcinoma | Recurrent Laryngeal Squamous Cell Carcinoma | Recurrent Oral Cavity Squamous Cell Carcinoma | Recurrent Oropharyngeal Squamous Cell Carcinoma | Resectable Oropharyngeal Squamous Cell CarcinomaUnited States
-
NeoImmuneTechRecruitingRecurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified | Refractory High Grade B-Cell Lymphoma | Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-cell LymphomaUnited States
-
NeoImmuneTechBristol-Myers SquibbTerminatedGastric or Gastro-esophageal Junction (GEJ) or Esophageal Adenocarcinoma (EAC)United States, Poland
-
NeoImmuneTechRoche Pharma AGActive, not recruitingCarcinoma, Non-Small-Cell Lung | Non-Small Cell Lung Cancer | Non Small Cell Lung Cancer | Nonsmall Cell Lung Cancer | Non-Small Cell Lung CarcinomaUnited States
-
NeoImmuneTechImmune Oncology NetworkTerminatedMelanoma | Merkel Cell Carcinoma | Cutaneous Squamous Cell CarcinomaUnited States
-
Genexine, Inc.Active, not recruitingRecurrent GlioblastomaKorea, Republic of
-
NeoImmuneTechMerck Sharp & Dohme LLCActive, not recruitingSmall Cell Lung Cancer | Pancreatic Cancer | Ovarian Cancer | Non Small Cell Lung Cancer | Triple Negative Breast Cancer | Microsatellite Stable Colorectal Cancer | Any Advanced Solid TumorsUnited States