Improving the Immune System With Human IL-7 Vaccine in Older Subjects Who Have Had Chemotherapy

• Status: Terminated
• Trial end date: 2016-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Background: Drugs given to treat cancer (chemotherapy) can weaken the human immune system. But it can also become weaker because of aging. Interleukin (IL)-7, a molecule produced naturally in the body, can help improve the function of the immune system. Researchers want to study the effects of IL-7 on immune system function in two different groups of older people. One group will be people who have received vaccines before IL-7. The other group will be people who have received Vaccines after IL-7.

Objectives: To evaluate the effect of IL-7 on the immune system responses to vaccines in older people following chemotherapy.

Eligibility: People at least 60 years of age who have recently finished chemotherapy for breast, colon, or bladder cancer.

Design:

• People in the study will be screened with a physical examination, medical history, and blood tests. Other screening tests, such as tumor imaging, may also need to be performed.

• Everyone will receive a series of five different vaccines commonly used to prevent diseases. We will compare the responses of people in Sequence 1 who will receive vaccines before IL-7 with the responses of people in Sequence 2 who received the same vaccines after IL-7.

• The vaccines will be given randomly in two Arms at different times.

• Arm 1: diphtheria and tetanus, polio, pneumonia (with two booster shots), hepatitis B (with two booster shots), and hepatitis A (with one booster shot),

• Arm 2: hepatitis A (with one booster shot), hepatitis B (with two booster shots), pneumococcal (with two booster shots), diphtheria and tetanus, polio, pneumonia (with two booster shots)

• There are 5 vaccines to be given to each subject, following one of two randomly assigned sequences of vaccine administration (Sequence 1 or Sequence 2).

• The first vaccine arm contains the two diphtheria protein containing vaccines tetanus and diphtheria (Td) and pneumococcal conjugate 13 (PCV13) and polio. The second vaccine arm contains the Hepatitis A and Hepatitis B vaccines. Subjects will either get tetanus, diphtheria, polio, and pneumonia vaccines before IL-7 therapy (Sequence 1) or hepatitis A and hepatitis B vaccines before IL-7 therapy (Sequence 2). The response to vaccines will be evaluated 4 weeks after vaccination. This will be followed by IL-7 therapy, then administration of the other group of vaccines. Therefore, subjects on both arms will receive the same set of vaccines, just at different times with respect to IL-7 therapy.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Heptavalent Pneumococcal Conjugate Vaccine; Vaccines

Criteria

• INCLUSION CRITERIA:

• Adults over the age of 60

• Documentation of positive diagnosis for any of the following:

• Non metastatic breast carcinoma following neo-adjuvant chemotherapy and appropriate surgery or following adjuvant radio / chemotherapy.

• Stage II or III colon carcinoma following appropriate surgery and adjuvant chemotherapy or following appropriate neoadjuvant chemoradiation/surgery and adjuvant chemotherapy.

• Stage II bladder carcinoma following neo-adjuvant chemotherapy and appropriate surgery or following adjuvant chemotherapy. Patients with recurrent tumors are not eligible.

• Appropriate therapy for each disease must be consistent with the latest National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology available at the web site: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp

• Completed cancer specific therapy (including surgery, radiotherapy and/or chemotherapy) a minimum of 4 weeks prior to entry. (Subjects with hormone receptor positive breast carcinoma maintained on hormonal therapy following chemotherapy and radiation are eligible).

• Completed cancer specific therapy at most 6 months prior to entry.

• Reasonable expectation that no chemotherapy will be given in the subsequent 6 months (Principal Investigators (PIs) discretion).

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the upper limit of normal.

• Bilirubin < 1.5.

• Absolute Neutrophil Count greater than l000 / mm(3).

• Platelet count greater than 75K.

• International normalized ratio (INR)/partial thromboplastin time (PTT) within 1.5 times upper limit of normal (Common Terminology Criteria in Adverse Events (CTCAE) 4.0 grade 1 abnormality is acceptable)

• Serum creatinine within 1.5 times upper limit of normal (CTCAE 4.0 grade 1 abnormality is acceptable)

• Creatine phosphokinase (CPK) within 2.5 times upper limit of normal (CTCAE 4.0 grade 1 abnormality is acceptable)

• Serum albumin greater or equal to 3g/dl (CTCAE 4.0 grade 1 abnormality is acceptable)

• Serum electrolytes within normal limits (CTCAE 4.0 grade 1 abnormality is acceptable)

• Karnofsky performance status greater or equal to 70%.

EXCLUSION CRITERIA FOR ALL PARTICIPANTS:

• Significant heart disease defined as:

• Significant coronary arterial disease

• myocardial infarction in the last 6 months, angina in the previous 3 months,

• Troponin elevation at level of myocardial infarction as defined by the manufacturer

• Ischemic changes on electrocardiogram (ECG)

• Atrio-ventricular block greater than 1st degree, in absence of pacemaker,

• Corrected QT interval (QTc) greater than 480ms (CTCAE 4.0 grade 1 abnormality is acceptable),

• History of ventricular arrhythmia,

• Left Ventricular Ejection Fraction below the institutional limit of normal,

• Positive serology for human T-lymphotropic viruses, type 1 (HTLV I), human immunodeficiency virus (HIV), hepatitis A, hepatitis B, or hepatitis C infection including a positive hepatitis B serology indicative of previous immunization (i.e. hepatitis B surface antibody (HBs Ab) positive and hepatitis B core antibody (HBc Ab) negative)

• History of autoimmune disease: patients with vitiligo or endocrine disease controlled by replacement therapy including, diabetes, thyroid and adrenal disease may be enrolled

• Patients requiring chronic immunosuppressive therapy (including corticosteroids) for any medical condition,

• Splenomegaly or history of proliferative hematologic disease

• Prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation

• Inability or refusal to practice contraception during therapy (as physiologically relevant)

• History of medical or psychiatric disease which, in the view of the principal investigator, would preclude safe treatment

• Cognitive impairment

• Serious bleeding diathesis or those who are on therapeutic anticoagulation

• Previous exposure to Hepatitis A or B vaccines

Patients who received a tetanus and diphtheria (Td) or tetanus, diphtheria- acelluar, pertussis (Tdap) immunization in the previous 5 years,

• History of anaphylaxis or serious allergic reactions to previous administration of any of the vaccines

• Known hypersensitivity to any of the following: diphtheria toxoid, neomycin, polymixin B, streptomycin, 2 phenoxyethanol, formaldehyde, aluminum hydroxide, yeast

• Patients who had received one or more doses of the pneumococcal polysaccharide vaccine 23 (PPSV23) vaccine in the previous 12 months

• Inability to give informed consent