Vaccine Response With NT-I7

NCT04054752 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 19013419-C-0134
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Carcinoma; Colorectal Adenocarcinoma; Bladder Carcinoma

Keywords

Breast Cancer; Colorectal Cancer; Immune Insufficiency; Bladder Cancer; Immunocompromised Host

Outcome Measures

Primary Outcomes (2)

• Phase 1: Safety of NT-I7 in elderly patients after chemotherapy

  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

  vaccine titers

  day 42 and day 106

Study Arms (3)

1/ Arm 1

EXPERIMENTAL

NT-I7 administered at 720 and 960g/kg to select the OBD of NT-I7

Biological: Recombinant human IL-7-hyFc (NT-I7)

2/ Arm 2a

ACTIVE COMPARATOR

Administration of 4 vaccines according to Sequence 1 + NT-I7 administration at OBD to assess vaccine response

Biological: Vaccine sequence 1

3/ Arm 2b

ACTIVE COMPARATOR

Administration of 4 vaccines according to Sequence 2 + NT-I7 administration at OBD to assess vaccine response

Biological: Vaccine sequence 2

Interventions

Recombinant human IL-7-hyFc (NT-I7) BIOLOGICAL

NT-I7 administered at escalating doses of 720, and 960g/kg to determine OBD of NT-I7

1/ Arm 1

Vaccine sequence 1 BIOLOGICAL

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

2/ Arm 2a

Vaccine sequence 2 BIOLOGICAL

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

3/ Arm 2b

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• NeoImmuneTech: collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Breast Neoplasms; Urinary Bladder Neoplasms; Colorectal Neoplasms

Interventions

efineptakin alfa

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Mustafa A Hyder, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2019
• First Posted: August 13, 2019
• Study Start: May 30, 2023
• Primary Completion: November 1, 2023
• Study Completion: November 1, 2023
• Last Updated: November 2, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)