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

Primary Purpose

Breast Cancer, Colon Cancer, Bladder Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Glycosylated Recombinant Human Interleukin-7
Diphtheria/Tetanus Vaccine
Polio Vaccine
Pneumococcal Vaccine
Hepatitis A Vaccine
Hepatitis B Vaccine
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Colorectal Cancer, Breast Cancer, Immunization, Immunocompromised Host, Bladder Cancer, Colon Cancer

Eligibility Criteria

60 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers
  • 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

Sites / Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike
  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A -Sequence 1 Immunizations

Arm B - Sequence 2 Immunizations

Arm Description

Receive vaccine of Sequence 1 first, then vaccines of Sequence 2, 7 weeks later, after receiving interleukin-7 (IL-7)

Receive vaccines of Sequence 2 first then vaccines of Sequence1, 7 weeks later, after receiving IL-7

Outcomes

Primary Outcome Measures

Evaluate and Quantify the Impact of Interleukin-7 (CYT107) Therapy on Specific Immune Responses to Vaccines (in Particular to Neo Antigens) in Older Subjects Following Chemotherapy

Secondary Outcome Measures

Evaluate and Quantify the Impact of Interleukin-7 (CYT107) Therapy on the T Cell Receptor Diversity in Older Subjects Following Chemotherapy
Evaluate the Effects of Interleukin-7 (CYT107) 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 Interleukin-7 (CYT107) Administration in a Broad, Mass Protection Strategy for an Aging Population
Number of Participants With Adverse Events
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

Full Information

First Posted
April 19, 2011
Last Updated
May 16, 2016
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01339000
Brief Title
Improving the Immune System With Human IL-7 Vaccine in Older Subjects Who Have Had Chemotherapy
Official Title
A Multicenter Phase II Study of Enhancement of Immune Reconstitution and Vaccine Responses With Administration of Glyco-Recombinant Human IL-7(CYT107) in Older Subjects Following Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Terminated
Why Stopped
Company supplying drug declared bankruptcy, thus there was no drug supply.
Study Start Date
April 2011 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
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 defects 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. Recombinant human interleukin-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. OBJECTIVES: - Evaluate and quantify the impact of interleukin-7 (CYT107) therapy on specific immune responses to each vaccine (in particular to neo antigens) in older subjects following chemotherapy. ELIGIBILITY: Adults over the age of 60. Diagnosis of non metastatic breast, bladder or colorectal 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. DESIGN: Subjects will be enrolled following the specific therapy for their respective diseases. Subjects will undergo immunizations with various antigens, randomized to be administered either before or after treatment with CYT107 The vaccines, randomly assigned to be administered before CYT107 therapy are administered four weeks before the start of CYT107 therapy. CYT107 is administered once a week for 3 doses (20 microg/kg/dose) via intramuscular route (IM) The vaccines, randomly assigned to be administered after CYT107 therapy are administered 17 days after the first dose of CYT107 therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Colon Cancer, Bladder Cancer
Keywords
Colorectal Cancer, Breast Cancer, Immunization, Immunocompromised Host, Bladder Cancer, Colon Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A -Sequence 1 Immunizations
Arm Type
Experimental
Arm Description
Receive vaccine of Sequence 1 first, then vaccines of Sequence 2, 7 weeks later, after receiving interleukin-7 (IL-7)
Arm Title
Arm B - Sequence 2 Immunizations
Arm Type
Experimental
Arm Description
Receive vaccines of Sequence 2 first then vaccines of Sequence1, 7 weeks later, after receiving IL-7
Intervention Type
Drug
Intervention Name(s)
Glycosylated Recombinant Human Interleukin-7
Intervention Description
Interleukin-7 (CYT 107) 20 microgram/kg / dose, by intramuscular (IM) injection
Intervention Type
Biological
Intervention Name(s)
Diphtheria/Tetanus Vaccine
Intervention Description
Diphtheria/Tetanus Vaccine will be administered according to the random schedule per protocol.
Intervention Type
Biological
Intervention Name(s)
Polio Vaccine
Intervention Description
Polio Vaccine will be administered according to the randomized schedule per protocol.
Intervention Type
Biological
Intervention Name(s)
Pneumococcal Vaccine
Intervention Description
Pneumococcal Vaccine will be administered according to the randomization schedule per protocol.
Intervention Type
Biological
Intervention Name(s)
Hepatitis A Vaccine
Intervention Description
Hepatitis A Vaccine will be administered according to the randomization schedule per protocol.
Intervention Type
Biological
Intervention Name(s)
Hepatitis B Vaccine
Intervention Description
Hepatitis B vaccine will be administered according to the randomization schedule per protocol.
Primary Outcome Measure Information:
Title
Evaluate and Quantify the Impact of Interleukin-7 (CYT107) Therapy on Specific Immune Responses to Vaccines (in Particular to Neo Antigens) in Older Subjects Following Chemotherapy
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Evaluate and Quantify the Impact of Interleukin-7 (CYT107) Therapy on the T Cell Receptor Diversity in Older Subjects Following Chemotherapy
Time Frame
10 weeks
Title
Evaluate the Effects of Interleukin-7 (CYT107) Therapy on the Quality of T Cell Specific Responses by Multiparameter Flow Cytometry
Time Frame
8 weeks
Title
Based on the First Two Primary Objectives, Consider and Discuss the Need for Larger Studies to Evaluate the Potential Benefit of Interleukin-7 (CYT107) Administration in a Broad, Mass Protection Strategy for an Aging Population
Time Frame
1 year
Title
Number of Participants With Adverse Events
Description
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ronald E Gress, M.D.
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
14139020
Citation
BOWMAN BU Jr, PATNODE RA. NEUTRALIZATION OF BACTERIOPHAGE PHI-X174 BY SPECIFIC ANTISERUM. J Immunol. 1964 Apr;92:507-14. No abstract available.
Results Reference
background
PubMed Identifier
5926449
Citation
Finkelstein MS, Uhr JW. Antibody formation. V. The avidity of gamma-M and gamma-G guinea pig antibodies to bacteriophage phi-x 174. J Immunol. 1966 Nov;97(5):565-76. No abstract available.
Results Reference
background
PubMed Identifier
14253517
Citation
ROLFE U, SINSHEIMER RL. ANTIGENS OF BACTERIOPHAGE PHI-X174. J Immunol. 1965 Jan;94:18-21. No abstract available.
Results Reference
background

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

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