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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01339000
First received: April 19, 2011
Last updated: November 4, 2014
Last verified: October 2014
  Purpose

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 recently completed chemotherapy treatment for breast, colon, or bladder cancer. The other group will be people who have never received chemotherapy.

Objectives:

- To evaluate the effect of IL-7 on the immune system response in older people who either have a normal immune system or have a weakened immune system following chemotherapy.

Eligibility:

  • People at least 60 years of age who have recently finished chemotherapy for breast, colon, or bladder cancer.
  • People at least 60 years of age who have never had chemotherapy (control group).

Design:

  • People in the study will be screened with a physical examination, medical history, and blood tests. Those who have cancer may have other screening tests, such as tumor imaging.
  • Everyone will receive a series of seven different vaccines commonly used to prevent diseases. We will compare the responses of people in the control group (who have a normal immune system and who will not receive any IL-7) with the responses the people who received the same vaccines with IL-7.
  • The vaccines will be given randomly in two groups at different times.
  • Group 1: diphtheria and tetanus, polio, and pneumonia (with two booster shots)
  • Group 2: hepatitis A (with one booster shot), hepatitis B (with two booster shots), influenza, and PhiX174 (a control vaccine used to test general immune response).
  • People who have had chemotherapy will also receive three weekly injections of an IL-7 drug. These injections will start 4 weeks after the first group of vaccines. The other group of vaccines will then be given 2 days after the last weekly injection. After each injection of IL-7, participants will provide blood samples for research and monitoring purposes.
  • Those in the control group will also provide regular blood samples for monitoring and research purposes.

Condition Intervention Phase
Breast Cancer
Colon Cancer
Bladder Cancer
Drug: Glycosylated Recombinant Human Interleukin-7
Biological: Tetanus Vaccine
Biological: Polio Vaccine
Biological: Pneumaococcal Vaccine
Biological: Hepatitis A Vaccine
Biological: Hepatitis B Vaccine
Biological: PhiX 174
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Phase II Study of Enhancement of Immune Reconstitution and Vaccine Responses With Administration of Glyco-Recombinant Human IL-7 in Older Subjects Following Chemotherapy

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Vaccines responses [ Time Frame: 8 weeks to 1 year ] [ Designated as safety issue: No ]
  • Quality of immune responses [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Safety of rhlL-7 [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: April 2011
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sequence 1
Receive vaccine of group 1 first, then vaccines of group 2, 7 weeks later, after receiving IL-7
Drug: Glycosylated Recombinant Human Interleukin-7
Glyco-rhIL-7 (CYT 107) 20 microgram/kg / dose, by subcutaneous injection
Biological: Tetanus Vaccine
Tetanus Vaccine will be administered according to the random schedule per protocol.
Biological: Polio Vaccine
Polio Vaccine will be administered according to the randomized schedule per protocol.
Biological: Pneumaococcal Vaccine
Pneumaococcal Vaccine will be administered according to the randomization schedule per protocol.
Biological: Hepatitis A Vaccine
Hepatitus A Vaccine will be administered according to the randomization schedule per protocol.
Biological: Hepatitis B Vaccine
Hapatitis A vaccine will be administered according to the randomization schedule per protocol.
Biological: PhiX 174
PHiX 174 Vaccine will be administered according to the rand schedule per protocol.
Experimental: Sequence 2
Receive vaccines of group 2 first then vaccines of group 1, 7 weeks later, after receiving IL-7
Drug: Glycosylated Recombinant Human Interleukin-7
Glyco-rhIL-7 (CYT 107) 20 microgram/kg / dose, by subcutaneous injection
Biological: Tetanus Vaccine
Tetanus Vaccine will be administered according to the random schedule per protocol.
Biological: Polio Vaccine
Polio Vaccine will be administered according to the randomized schedule per protocol.
Biological: Pneumaococcal Vaccine
Pneumaococcal Vaccine will be administered according to the randomization schedule per protocol.
Biological: Hepatitis A Vaccine
Hepatitus A Vaccine will be administered according to the randomization schedule per protocol.
Biological: Hepatitis B Vaccine
Hapatitis A vaccine will be administered according to the randomization schedule per protocol.
Biological: PhiX 174
PHiX 174 Vaccine will be administered according to the rand schedule per protocol.

Detailed 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 naive and memory T cell subsets.
  • The clinical implications of the kinetics, nature and extent of immune reconstitution defect following standard or ablative chemotherapy in older adults with cancer (in particular the lack of reconstitution of large pools naive T cell with broad repertoire diversity and of memory T cells) are not fully appreciated.
  • 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 may be misjudged or altogether overlooked.
  • 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.

OBJECTIVES:

  • Determine whether the use of glyco-rhIL-7 impacts the overall immune response to a set of 6 vaccines to be given to patients with cancer.
  • Evaluate and quantify the impact of glyco-rhIL-7 therapy on specific immune responses to each vaccine (in particular to neo antigens) in older subjects following chemotherapy.
  • Compare the vaccine responses in the groups where the vaccines are given before or after glyco-rhIL-7 in cancer patients to those in a third group of age matched healthy volunteers not receiving glyco-rhIL-7.
  • Evaluate the effects of glyco-rhIL-7 therapy on passive memory immune responses (i.e. when not re-stimulated with in vivo recall antigen).
  • Evaluate and quantify the impact of glyco-rhIL-7 therapy on the T cell receptor diversity in older subjects following chemotherapy.
  • Evaluate the effects of glyco-rhIL-7 therapy on the quality of T cell specific responses by multiparameter flow cytometry.
  • Based on the first two primary objectives, consider and discuss the need for larger studies to evaluate the potential benefit of glyco-rhIL-7 administration in a broad, mass protection strategy for an aging population.

ELIGIBILITY:

  • Adults over the age of 60.
  • Diagnosis of non metastatic breast, bladder or colon cancer following adjuvant / neo-adjuvant chemotherapy.
  • Completed a treatment with chemotherapy a minimum of 4 weeks prior to entry.
  • Reasonable expectation that no chemotherapy will be given in the subsequent 6 months.
  • An age-matched healthy control cohort will be enrolled as well.

DESIGN:

  • Subjects will be enrolled following the specific therapy for their respective diseases or as age-matched healthy controls.
  • Subjects will undergo immunizations with various antigens, randomized to be administered either before or after treatment with glyco-rhIL-7 (healthy controls will not receive rhIL-7).
  • The vaccines, randomly assigned to be administered before glyco-rhIL-7 therapy are administered four weeks before the start of glyco-rhIL-7 therapy.
  • Glyco-rhIL-7 is administered once a week for 3 doses (20 microg/kg/dose subcutaneously)
  • The vaccines, randomly assigned to be administered after glyco-rhIL-7 therapy are administered 17 days after the first dose of glyco-rhIL-7 therapy.
  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

For cancer patients

  • 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 (Dukes B or C) colon carcinoma following appropriate surgery and adjuvant chemotherapy.
  • Stage II bladder carcinoma following neo-adjuvant radio / chemotherapy and appropriate surgery or following adjuvant radio / chemotherapy. Patients with recurrent tumors are not eligible.
  • Appropriate therapy for each disease must be consistent with the latest 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 (PI s discretion).
  • AST and ALT < 3 times the upper limit of normal.
  • Bilirubin < 1.5 (except in cases of Gilbert's disease).
  • Absolute Neutrophil Count greater than l000 / mm(3).
  • Platelet count greater than 75K.
  • INR/PTT within 1.5 times upper limit of normal (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)
  • 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%.

For healthy volunteers

  • Adults over the age of 60.
  • CBC with differential, Electrolytes, BUN and Creatinine, Liver panel, mineral panel, all within normal limits for age or, at most, a CTCAE 4.0 grade 1 abnormality,
  • Absolute Neutrophil Count greater than l000 / mm(3).
  • Platelet count greater than 75K.
  • Karnofsky performance status greater or equal to 70%.
  • Subjects with chronic but adequately treated and stable medical conditions (such as stable hypertension, hyperlipidemia, diabetes, hypothyroidism, etc) may be eligible (PI discretion): stable medical condition defined as no hospitalization, no new diagnoses and no significant adjustment of medications in the 3 months preceding enrollment.

EXCLUSION CRITERIA FOR ALL PARTICIPANTS:

  • Subjects with 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 ECG
  • Atrio-ventricular block greater than 1st degree, in absence of pacemaker,
  • 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 HTLV I, HIV, hepatitis B, or hepatitis C infection including a positive hepatitis B serology indicative of previous immunization (i.e. HBs Ab positive and HBc Ab negative),
  • Life expectancy of less than 6 months,
  • 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,
  • Patients with 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,
  • Patient with cognitive impairment,
  • Previous exposure to Hepatitis A or B vaccines,
  • Subjects who received a DT 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,
  • Subjects with a history of allergy to influenza vaccine may still participate in the study but will not receive the influenza vaccine,
  • Inability to give informed consent.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01339000

Contacts
Contact: Ronald E Gress, M.D. (301) 496-1791 gressr@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Sponsors and Collaborators
Investigators
Principal Investigator: Ronald E Gress, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01339000     History of Changes
Other Study ID Numbers: 110146, 11-C-0146
Study First Received: April 19, 2011
Last Updated: November 4, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Immune Reconstitution
Recombinant Interleukin-7
Immunization
Immunocompromised Host
Breast Cancer
Colon Cancer
Bladder Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Urinary Bladder Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Urinary Bladder Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms

ClinicalTrials.gov processed this record on November 24, 2014