- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04054752
Vaccine Response With NT-I7
A Phase 1/1b Study of Enhancement of Immune Reconstitution and Vaccine Responses With Administration of Recombinant Human IL-7-hyFc (NT-I7) in Older Subjects Following Chemotherapy
Background:
People with cancer, and especially older people, have a weakened immune system (the defense system of the body). This is often caused by the treatments for cancer. Older cancer survivors are therefore more prone to getting infections, some of which are preventable through vaccines. But because their immune systems are weakened, their response to vaccines is poor. Researchers want to see if a new drug, NT-I7, can help.
Objective:
To see if NT-I7 can boost the immune system.
Eligibility:
Adults 60 and older who have recently finished chemotherapy for breast, colorectal, or bladder cancer.
Design:
Participants will be screened with a physical exam, medical history, and blood and urine samples. Their heart s electrical activity will be checked. They will have an ultrasound of their spleen. They may give a tissue sample from a previous biopsy.
Participants in phase 1a of the study will get 1 dose of NT-I7. It will be given by injection with a needle into the muscle of the upper arm, thigh, or buttocks.
Participants in phase 1b will get 5 vaccines over a few months. They may get an optional booster and/or 6th vaccine. They will also get NT-I7.
Participants will repeat the screening tests during the study. They may get a peripheral intravenous catheter in a vein in their hand or arm for blood draws.
Participants may have apheresis. For this, blood is taken from an arm vein. The white blood cells are separated from the blood. The rest of the blood, minus the white blood cells, is returned into a vein in the other arm. A catheter may be used.
Participants will have follow-up visits for 1 year.
Study Overview
Status
Intervention / Treatment
Detailed Description
Background:
Interleukin-7 is a homeostatic cytokine with a critical role in lymphoid homeostasis through which it exerts its immune-restorative effects, particularly re-expansion of the na(SqrRoot) ve and memory T-cell subsets.
The clinical implications of the kinetics, nature and extent of immune reconstitution defects following standard or ablative chemotherapy in older adults with cancer (in particular the lack of reconstitution of large pools of na(SqrRoot) ve T-cell with broad repertoire diversity and of memory T-cells) are not well characterized.
As chemotherapy often induces only temporary complete or partial disease responses but no cure, candidates for novel immunotherapy strategies may be significantly impeded in their responses to active immunotherapy attempts, the therapeutic potential of which is becoming increasingly utilized.
Recombinant human IL-7 (rhIL-7) may play a role in immune reconstitution and immune enhancement in various circumstances of immune insufficiency in older individuals following chemotherapy or in the context of enhancing cancer immunotherapy or during immune senescence.
Elderly cancer survivors are vulnerable to vaccine-preventable diseases and are known to have poor anti-vaccine-specific immune responses. Effective prevention of communicable diseases is important for cancer survivorship.
This study will use NT-I7, a long acting IL-7 cytokine, composed of human IL-7 and a hybrid Fc (hyFc) region to extend half-life.
Objectives:
Phase 1: Select optimal biological dose (OBD) of NT-I7 in older subjects with breast, bladder, prostate or a gastrointestinal cancer following chemotherapy.
Phase 1b: Evaluate and quantify the functional impact of NT-I7 therapy on specific immune responses to selected vaccines in older subjects following chemotherapy.
Eligibility:
Adults greater than or equal to 60 year of age.
Diagnosis of non-metastatic breast, bladder or a gastrointestinal cancer following adjuvant / neo-adjuvant chemotherapy; or metastatic breast, gastrointestinal or prostate cancer after chemotherapy.
Completed a treatment with chemotherapy a minimum of 4 weeks and no more than 12 months prior to entry with no evidence of disease.
Reasonable expectation that no cancer-specific therapy will be given in the subsequent 6 months.
Design:
Subjects will be enrolled into this single center Phase 1/1b study following the specific therapy for their respective diseases.
In Phase 1 part of the study, two dose levels, 720 micro g/kg and 960 micro g/kg, will be compared. Six subjects will be enrolled in each dose level, and a single dose of NT-I7 will be delivered intramuscularly. The purpose of this part of the study is to select the OBD.
OBD is defined as the dose that yields the greatest rise in peak absolute total T-cell counts (peak value at any timepoint during the first 28 days post NT-I7 administration) with corresponding rise in na(SqrRoot) ve subsets of CD4+ and CD8+ T cells without accompanying substantial toxicities. Absolute increase is a delta between the baseline counts and the peak counts within each subject.
Once OBD is determined, the Phase 1b portion of this study will begin. Subjects will undergo immunizations with various antigens, randomized to be administered either before or after a single dose of NT-I7 at OBD. This inter-subject randomization of the order in which the immunizations are administered (according to the Sequence 1 or to the Sequence 2 schedule) will allow all immunocompromised subjects entered on the Phase 1b portion of the study to receive NT-I7.
The vaccines, randomly assigned to be administered before NT-I7 therapy are administered six weeks before the administration of NT-I7 therapy.
The vaccines, randomly assigned to be administered after NT-I7 therapy are administered 3 weeks after NT-I7 injection.
Study Type
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Mustafa A Hyder, M.D.
- Phone Number: (240) 858-3182
- Email: mustafa.hyder@nih.gov
Study Locations
-
-
Maryland
-
Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
- INCLUSION CRITERIA:
- Age greater than or equal to 60 years
Documentation of positive diagnosis based on pathology/histology report (no need for archival tissue or new biopsy) for any of the following:
- Stage I-III breast carcinoma following neo-adjuvant/adjuvant chemotherapy and appropriate surgery and/or radiotherapy.
- Stage II or III gastrointestinal cancer following appropriate surgery and adjuvant chemotherapy or following appropriate neoadjuvant chemoradiation/surgery and adjuvant chemotherapy.
- Stage II or III bladder carcinoma following neo-adjuvant chemotherapy and appropriate surgery or following adjuvant chemotherapy.
- Stage IV breast, gastrointestinal, or prostate cancer, following surgery and chemotherapy, or chemotherapy alone
NOTE: "Appropriate therapy" for each disease must be consistent with NCCN Clinical Practice Guidelines in Oncology available at the time of treatment in the opinion of the investigator (http://www.nccn.org/professionals/physician_gls/f_guidelines.asp)
- Completed cancer specific therapy (including surgery, radiotherapy and/or systemic therapy) at least 4 weeks and no more than 12 months prior to registration. (Subjects with hormone receptor positive breast carcinoma maintained on hormonal therapy following chemotherapy and radiation are eligible. Subjects with HER2 positive breast carcinoma maintained on anti-HER2 agents after definitive therapies are also eligible).
- Reasonable expectation that no cancer-specific therapy, with the exception noted in the previous criteria, will be given in the subsequent 6 months (PI's discretion).
Adequate organ function, as follows:
- AST/ALT: < 3 times upper limit of normal (ULN)
- Bilirubin: < 1.5 times ULN
- Absolute Neutrophil Count: > 1000/mm3
- Platelet count: > 75,000/mm3
- INR/PTT: <1.5 times ULN
- Serum Creatinine: <1.5 times ULN
- CPK: <2.5 times ULN
- Serum albumin: greater than or equal to 3g/dL
- Serum electrolytes: within normal limits
- Karnofsky performance status greater or equal to 70%
Effects of NT-I7 on the developing human fetus are unknown. For these reasons the following measures apply:
- Subjects enrolled on the study must not be planning to father children within the projected duration of the trial, starting with the pre-screening/screening visit through 120 days after the administration of NT-I7.
- Men with partners of childbearing potential (defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal (i.e., amenorrheic for greater than or equal to 12 months without alternative medical cause) must use effective contraception prior to study entry, and for 120 days after the administration of NT-I7.
- Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, the study participants' treating physician should be informed immediately.
EXCLUSION CRITERIA:
- Subjects who are receiving any other investigational agents
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Significant heart disease defined as:
- Significant coronary arterial disease
- Myocardial infarction in the last 6 months, angina in the previous 3 months
- Troponin elevation above reference range set by each institution where the troponin measurement was performed.
- Ischemic changes on ECG
- Atrio-ventricular block greater than 1st degree, in absence of pacemaker
- QTc (using Fridericia and Framingham correction formula) greater than 480ms (CTCAE 5.0 grade 1 abnormality is acceptable)
- History of ventricular arrhythmia
- Left Ventricular Ejection Fraction of less than 50% determined by echocardiography
- Positive serology for HTLV-I or HIV, or serology findings indicative of ongoing infection with hepatitis A, hepatitis B, or hepatitis C. Subjects with serology findings indicative of previous exposure to hepatitis A or B vaccination will not be excluded from Phase 1 part of the study but will be excluded from Phase 1b part of the study (see below for additional exclusion criteria for the Phase-1b part of the study only).
- History of autoimmune disease EXCEPT for the following: subjects with vitiligo or endocrine disease controlled by replacement therapy including diabetes, thyroid, and adrenal disease may be enrolled
- Subjects requiring chronic immunosuppressive therapy (including corticosteroids above physiologic replacement dosage) for any medical condition. We will permit 1) systemic corticosteroids at physiologic replacement dosage which are not to exceed 10 mg/day of prednisone or an equivalent, 2) intranasal or inhaled corticosteroids, 3) intraarticular injection of corticosteroids, 4) topical corticosteroids, 5) or a short-term use of systemic corticosteroids greater than 10 mg/day of prednisone or an equivalent for 10 days or less.
- Splenomegaly or history of proliferative hematologic disease
- Prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation
- History of medical or psychiatric disease, or cognitive impairment, which, in the view of the principal investigator would preclude safe treatment
- Serious bleeding diathesis based on clinical history of significant bleeding attributed to coagulation/bleeding disorders, documentation of abnormal coagulation factors/platelet function studies at the discretion of PI, or those who are on therapeutic anticoagulation
- Inability to give informed consent
- Subjects who have received immune checkpoint inhibitors in the previous 12 months, or subjects who have received immunomodulatory drugs in the previous 4 weeks for any medical indications. Subjects who have received intravesical BCG administration for non-muscle invasive bladder cancer will be included in this study (i.e., not one of exclusion criteria).
Additional exclusion criteria for the Phase-1b part of the study only are as follows:
- Known hypersensitivity to any of the following: diphtheria toxoid, neomycin, polymixin B, streptomycin, 2 phenoxyethanol, formaldehyde, aluminum hydroxide, yeast
- Previous exposure to Hepatitis A or B vaccines or history of hepatitis A or B infection
- Subjects who received a Td or Tdap immunization in the previous 5 years
- History of anaphylaxis or serious allergic reactions to previous administration of any of the vaccines
- Subjects who had received one or more doses of the PPSV23 vaccine in the previous 12 months
- Latex allergy
- A history of Guillain-Barre syndrome within six weeks of administration of previous tetanus toxoid containing vaccines.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1/ Arm 1
NT-I7 administered at 720 and 960g/kg to select the OBD of NT-I7
|
NT-I7 administered at escalating doses of 720, and 960g/kg to determine OBD of NT-I7
|
Active Comparator: 2/ Arm 2a
Administration of 4 vaccines according to Sequence 1 + NT-I7 administration at OBD to assess vaccine response
|
Day 1 Immunization Pre-NT-I7:Td and Polio Day 64, Immunization Post-NT-I7: Hep A#1, Hep B#1 Day 106: Hep B#2 (Optional) 6 Month Post NT-I7 Vaccines (Optional): Polio, Hep A#2, Hep #3, PPSV23#1
|
Active Comparator: 3/ Arm 2b
Administration of 4 vaccines according to Sequence 2 + NT-I7 administration at OBD to assess vaccine response
|
Day 1 Immunization Pre-NT-I7: Hep A#1, Hep B#1 Day 64, Immunization Post-NT-I7:Td and Polio Day 106: no Vaccine 6 Month Post NT-I7 Vaccines (Optional): Polio, Hep A#2, Hep #3, PPSV23#1
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1: Safety of NT-I7 in elderly patients after chemotherapy
Time Frame: 28 days after treatment
|
List of adverse events and frequency
|
28 days after treatment
|
Phase 1b: Evaluate and quantify if NT-I7 at optimal biological dose (OBD) has impacts on specific immune responses to vaccines
Time Frame: day 42 and day 106
|
vaccine titers
|
day 42 and day 106
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Mustafa A Hyder, M.D., National Cancer Institute (NCI)
Publications and helpful links
Helpful Links
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
- Skin Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Urologic Diseases
- Neoplasms, Glandular and Epithelial
- Urinary Bladder Diseases
- Breast Diseases
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Breast Neoplasms
- Carcinoma
- Urinary Bladder Neoplasms
- Physiological Effects of Drugs
- Immunologic Factors
- Vaccines
Other Study ID Numbers
- 190134
- 19-C-0134
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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 Breast Carcinoma
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)CompletedInvasive Breast Carcinoma | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Estrogen Receptor Negative | Estrogen Receptor Positive | Lobular Breast Carcinoma | Postmenopausal | Ductal Breast Carcinoma | Ductal Breast Carcinoma In SituUnited States
-
National Cancer Institute (NCI)Active, not recruitingBreast Ductal Carcinoma In Situ | Invasive Breast Carcinoma | Multicentric Breast Carcinoma | Multifocal Breast Carcinoma | Synchronous Bilateral Breast CarcinomaUnited States, France, Spain, Canada, Saudi Arabia, Puerto Rico, Korea, Republic of, Ireland, Colombia, Mexico
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedMale Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Ductal Breast Carcinoma in Situ | Lobular Breast Carcinoma in SituUnited States
-
Mayo ClinicNational Cancer Institute (NCI)Active, not recruitingEstrogen Receptor Positive | Ductal Breast Carcinoma In Situ | Grade 1 Invasive Breast Carcinoma | Grade 2 Invasive Breast Carcinoma | Grade 3 Invasive Breast Carcinoma | Invasive Ductal and Lobular Carcinoma In Situ | Mucinous Breast Carcinoma | Tubular Breast CarcinomaUnited States
-
Northwestern UniversityNational Cancer Institute (NCI)RecruitingCancer Survivor | Invasive Breast Carcinoma | Ductal Breast Carcinoma In SituUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); Cianna Medical, Inc.TerminatedStage I Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIC Breast Cancer | Lobular Breast Carcinoma In Situ | Estrogen Receptor Negative | Estrogen Receptor Positive | HER2/Neu Negative | Progesterone Receptor Positive | Ductal Breast Carcinoma In Situ | Mucinous Breast Carcinoma | Tubular Breast Carcinoma and other conditionsUnited States
-
Ohio State University Comprehensive Cancer CenterWithdrawnStage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast Cancer | Ductal Breast Carcinoma in Situ | Lobular Breast Carcinoma in Situ
-
University of Southern CaliforniaNational Cancer Institute (NCI); California Breast Cancer Research ProgramCompletedStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Ductal Breast Carcinoma in Situ | BRCA1 Mutation Carrier | BRCA2 Mutation Carrier | Lobular Breast Carcinoma in SituUnited States
-
Case Comprehensive Cancer CenterWithdrawnStage I Breast Cancer | HER2-positive Breast Cancer | Male Breast Cancer | Stage II Breast Cancer | Estrogen Receptor-negative Breast Cancer | Estrogen Receptor-positive Breast Cancer | Progesterone Receptor-negative Breast Cancer | Progesterone Receptor-positive Breast Cancer | HER2-negative Breast... and other conditionsUnited States
-
Sunnybrook Health Sciences CentreActive, not recruitingBreast Cancer | Invasive Lobular Breast Carcinoma | Invasive Ductal Breast CarcinomaCanada
Clinical Trials on Recombinant human IL-7-hyFc (NT-I7)
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); Cancer Immunotherapy Trials Network (CITN)TerminatedHIV Infection | Kaposi Sarcoma | AIDS-Related Kaposi SarcomaUnited States
-
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
-
PT Kalbe Genexine BiologicsGenexine, Inc.Recruiting
-
Genexine, Inc.Terminated
-
National Institute of Allergy and Infectious Diseases...NeoImmune TechNot yet recruitingIdiopathic CD4 LymphopeniaUnited States
-
NeoImmuneTechNational Institute of Allergy and Infectious Diseases (NIAID); University of...Terminated
-
Genexine, Inc.CompletedHuman PapillomavirusKorea, Republic of
-
Mayo ClinicMerck Sharp & Dohme LLC; NeoImmune TechRecruitingRecurrent Glioblastoma, IDH-Wildtype | Recurrent Gliosarcoma | High Grade Astrocytic TumorUnited 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