Improving the Immune System With Human IL-7 Vaccine in Older Subjects Who Have Had Chemotherapy
| Status: | Terminated |
|---|---|
| Conditions: | Breast Cancer, Colorectal Cancer, Cancer, Cancer, Cancer, Cancer, Bladder Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 60 - 100 |
| Updated: | 4/21/2016 |
| Start Date: | April 2011 |
| End Date: | April 2016 |
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
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 (Td and
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.
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 (Td and
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.
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.
- 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 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.
- 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.
- 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 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.
- 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 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.
- 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%.
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 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 A, 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)
- 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 Td or 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 PPSV23 vaccine in the previous 12
months
- Inability to give informed consent
We found this trial at
2
sites
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: (888) NCI-1937
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