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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


Phase 2
60 Years
N/A
Open (Enrolling)
Both
Breast Cancer, Colon Cancer, Bladder Cancer

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Trial Information

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


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.

Inclusion 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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Vaccines responses

Outcome Time Frame:

8 weeks to 1 year

Safety Issue:

No

Principal Investigator

Claude Sportes, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

110146

NCT ID:

NCT01339000

Start Date:

April 2011

Completion Date:

April 2015

Related Keywords:

  • Breast Cancer
  • Colon Cancer
  • Bladder Cancer
  • Immune Reconstitution
  • Recombinant Interleukin-7
  • Immunization
  • Immunocompromised Host
  • Breast Cancer
  • Colon Cancer
  • Bladder Cancer
  • Urinary Bladder Neoplasms
  • Breast Neoplasms
  • Colonic Neoplasms

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892
Memorial Sloan Kettering Cancer CenterNew York, New York  10021