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
- 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.
- 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
- 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.
- Adults over the age of 60.
- Diagnosis of non metastatic breast, bladder or colon cancer following adjuvant /
- 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.
- 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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
8 weeks to 1 year
Claude Sportes, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|