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.
• 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.