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

Phase 2

Terminated

• Conditions: Breast Cancer; Colon Cancer; Bladder Cancer
• Interventions: Drug: Glycosylated Recombinant Human Interleukin-7; Biological: Diphtheria/Tetanus Vaccine; Biological: Polio Vaccine; Biological: Pneumococcal Vaccine; Biological: Hepatitis A Vaccine; Biological: Hepatitis B Vaccine

• Registration Number: NCT01339000
• Lead Sponsor: National Cancer Institute (NCI)

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.

Study Timeline

• Study Start: 2011-04
• Study First Submitted: 2011-04-19
• Study First Submitted QC: 2011-04-19
• Study First Posted: 2011-04-20
• Primary Completion: 2016-04
• Study Completion: 2016-04
• Status Verified: 2016-05
• Results First Submitted: 2016-05-16
• Results First Submitted QC: 2016-05-16
• Last Update Submitted: 2016-05-16
• Results First Posted: 2016-06-22
• Last Update Posted: 2016-06-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B - Sequence 2 Immunizations	Polio Vaccine	Receive vaccines of Sequence 2 first then vaccines of Sequence1, 7 weeks later, after receiving IL-7
Arm A -Sequence 1 Immunizations	Polio Vaccine	Receive vaccine of Sequence 1 first, then vaccines of Sequence 2, 7 weeks later, after receiving interleukin-7 (IL-7)
Arm A -Sequence 1 Immunizations	Hepatitis B Vaccine	Receive vaccine of Sequence 1 first, then vaccines of Sequence 2, 7 weeks later, after receiving interleukin-7 (IL-7)
Arm B - Sequence 2 Immunizations	Pneumococcal Vaccine	Receive vaccines of Sequence 2 first then vaccines of Sequence1, 7 weeks later, after receiving IL-7
Arm A -Sequence 1 Immunizations	Diphtheria/Tetanus Vaccine	Receive vaccine of Sequence 1 first, then vaccines of Sequence 2, 7 weeks later, after receiving interleukin-7 (IL-7)
Arm A -Sequence 1 Immunizations	Pneumococcal Vaccine	Receive vaccine of Sequence 1 first, then vaccines of Sequence 2, 7 weeks later, after receiving interleukin-7 (IL-7)
Arm B - Sequence 2 Immunizations	Glycosylated Recombinant Human Interleukin-7	Receive vaccines of Sequence 2 first then vaccines of Sequence1, 7 weeks later, after receiving IL-7
Arm B - Sequence 2 Immunizations	Hepatitis B Vaccine	Receive vaccines of Sequence 2 first then vaccines of Sequence1, 7 weeks later, after receiving IL-7
Arm A -Sequence 1 Immunizations	Hepatitis A Vaccine	Receive vaccine of Sequence 1 first, then vaccines of Sequence 2, 7 weeks later, after receiving interleukin-7 (IL-7)
Arm B - Sequence 2 Immunizations	Diphtheria/Tetanus Vaccine	Receive vaccines of Sequence 2 first then vaccines of Sequence1, 7 weeks later, after receiving IL-7
Arm B - Sequence 2 Immunizations	Hepatitis A Vaccine	Receive vaccines of Sequence 2 first then vaccines of Sequence1, 7 weeks later, after receiving IL-7
Arm A -Sequence 1 Immunizations	Glycosylated Recombinant Human Interleukin-7	Receive vaccine of Sequence 1 first, then vaccines of Sequence 2, 7 weeks later, after receiving interleukin-7 (IL-7)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Evaluate the Effects of Interleukin-7 (CYT107) Therapy on the Quality of T Cell Specific Responses by Multiparameter Flow Cytometry	8 weeks
Evaluate and Quantify the Impact of Interleukin-7 (CYT107) Therapy on the T Cell Receptor Diversity in Older Subjects Following Chemotherapy	10 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	Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

Trial Locations

Locations (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike; 🇺🇸 Bethesda, Maryland, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States