Vaccine Response With NT-I7

Breast Carcinoma Clinical Trial

Official title: 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

Status Withdrawn

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Bladder Carcinoma
• Breast Carcinoma
• Breast Neoplasms
• Carcinoma
• Colorectal Adenocarcinoma
• Urinary Bladder Neoplasms

• NCT number: NCT04054752
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Withdrawn
• Phase: Phase 1
• Start date: May 30, 2023
• Completion date: November 1, 2023