Improving the Immune System With Human IL-7 Vaccine in Older Subjects Who Have Had Chemotherapy
Condition: Breast Cancer; Colon Cancer; Bladder Cancer
MeSH terms: Colonic Neoplasms; Urinary Bladder Neoplasms
Intervention: Glycosylated Recombinant Human Interleukin-7; Diphtheria/Tetanus Vaccine; Polio Vaccine; Pneumococcal Vaccine; Hepatitis A Vaccine; Hepatitis B Vaccine
Intervention description: Interleukin-7 (CYT 107) 20 microgram/kg / dose, by intramuscular (IM) injection; Diphtheria/Tetanus Vaccine will be administered according to the random schedule per protocol.; Polio Vaccine will be administered according to the randomized schedule per protocol.; Pneumococcal Vaccine will be administered according to the randomization schedule per protocol.; Hepatitis A Vaccine will be administered according to the randomization schedule per protocol.; Hepatitis B vaccine will be administered according to the randomization schedule per protocol.
Intervention MeSH terms: Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 60 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Colorectal Cancer; Breast Cancer; Immunization; Immunocompromised Host; Bladder Cancer; Colon Cancer

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.
    

Eligibility 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