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

NCT01339000 | Terminated Phase 2 Results

• 2 other identifiers: 11014611-C-0146
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

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.

Conditions

Breast Cancer; Colon Cancer; Bladder Cancer

Keywords

Colorectal Cancer; Breast Cancer; Immunization; Immunocompromised Host; Bladder Cancer; Colon Cancer

Outcome Measures

Primary Outcomes (1)

• 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

  8 weeks

Secondary Outcomes (4)

• Evaluate and Quantify the Impact of Interleukin-7 (CYT107) Therapy on the T Cell Receptor Diversity in Older Subjects Following Chemotherapy

  10 weeks

• Evaluate the Effects of Interleukin-7 (CYT107) Therapy on the Quality of T Cell Specific Responses by Multiparameter Flow Cytometry

  8 weeks

• 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

  1 year

• Number of Participants With Adverse Events

  12 months

Study Arms (2)

Arm A -Sequence 1 Immunizations

EXPERIMENTAL

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

Drug: Glycosylated Recombinant Human Interleukin-7; Biological: Diphtheria/Tetanus Vaccine; Biological: Polio Vaccine; Biological: Pneumococcal Vaccine; Biological: Hepatitis A Vaccine; Biological: Hepatitis B Vaccine

Arm B - Sequence 2 Immunizations

EXPERIMENTAL

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

Drug: Glycosylated Recombinant Human Interleukin-7; Biological: Diphtheria/Tetanus Vaccine; Biological: Polio Vaccine; Biological: Pneumococcal Vaccine; Biological: Hepatitis A Vaccine; Biological: Hepatitis B Vaccine

Interventions

Glycosylated Recombinant Human Interleukin-7 DRUG

Interleukin-7 (CYT 107) 20 microgram/kg / dose, by intramuscular (IM) injection

Arm A -Sequence 1 Immunizations; Arm B - Sequence 2 Immunizations

Diphtheria/Tetanus Vaccine BIOLOGICAL

Diphtheria/Tetanus Vaccine will be administered according to the random schedule per protocol.

Arm A -Sequence 1 Immunizations; Arm B - Sequence 2 Immunizations

Polio Vaccine BIOLOGICAL

Polio Vaccine will be administered according to the randomized schedule per protocol.

Arm A -Sequence 1 Immunizations; Arm B - Sequence 2 Immunizations

Pneumococcal Vaccine BIOLOGICAL

Pneumococcal Vaccine will be administered according to the randomization schedule per protocol.

Arm A -Sequence 1 Immunizations; Arm B - Sequence 2 Immunizations

Hepatitis A Vaccine BIOLOGICAL

Hepatitis A Vaccine will be administered according to the randomization schedule per protocol.

Arm A -Sequence 1 Immunizations; Arm B - Sequence 2 Immunizations

Hepatitis B Vaccine BIOLOGICAL

Hepatitis B vaccine will be administered according to the randomization schedule per protocol.

Arm A -Sequence 1 Immunizations; Arm B - Sequence 2 Immunizations

Eligibility Criteria

• Age: 60 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Related Publications (3)

• BOWMAN BU Jr, PATNODE RA. NEUTRALIZATION OF BACTERIOPHAGE PHI-X174 BY SPECIFIC ANTISERUM. J Immunol. 1964 Apr;92:507-14. No abstract available.

  PMID: 14139020 BACKGROUND

• 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.

  PMID: 5926449 BACKGROUND

• ROLFE U, SINSHEIMER RL. ANTIGENS OF BACTERIOPHAGE PHI-X174. J Immunol. 1965 Jan;94:18-21. No abstract available.

  PMID: 14253517 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Colonic Neoplasms; Urinary Bladder Neoplasms; Colorectal Neoplasms

Interventions

Diphtheria-Tetanus Vaccine; Pneumococcal Vaccines; Hepatitis A Vaccines; Hepatitis B Vaccines

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Diphtheria Toxoid; Toxoids; Tetanus Toxoid; Vaccines, Combined; Streptococcal Vaccines; Viral Hepatitis Vaccines; Viral Vaccines

Limitations and Caveats

The company supplying interleukin-7 (IL-7) declared bankruptcy, thus the study was closed due to lack of drug supply.

Results Point of Contact

• Title: Dr. Ronald Gress
• Organization: National Cancer Institute

gressr@mail.nih.gov

301-496-1791

Study Officials

• Ronald E Gress, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 19, 2011
• First Posted: April 20, 2011
• Study Start: April 1, 2011
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: June 22, 2016
• Results First Posted: June 22, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)