Vaccine Response With NT-I7

Summary

Participation Requirements

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 reconstitu...

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 of naive T-cell with broad repertoire diversity and of memory T-cells) are not well characterized. 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 is becoming increasingly utilized. Recombinant human TL-7 (rhTL-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. Elderly cancer survivors are vulnerable to vaccine-preventable diseases and are known to have poor anti-vaccine-specific immune responses. Effective prevention of communicable diseases is important for cancer survivorship. This study will use NT-T7, a long acting TL-7 cytokine, composed of human TL-7 and a hybrid Fc (hyFc) region to extend half-life. Objectives: Phase 1: Select optimal biological dose (OBD) of NT-T7 in older subjects with breast, bladder, prostate or a gastrointestinal cancer following chemotherapy. Phase 1b: Evaluate and quantify the functional impact of NT-T7 therapy on specific immune responses to selected vaccines in older subjects following chemotherapy. Eligibility: Adults greater than or equal to 60 year of age. Diagnosis of non-metastatic breast, bladder or a gastrointestinal cancer following adjuvant/ neo-adjuvant chemotherapy; or metastatic breast, gastrointestinal or prostate cancer after chemotherapy. Completed a treatment with chemotherapy a minimum of 4 weeks prior to entry with no evidence of disease. Reasonable expectation that no cancer-specific therapy will be given in the subsequent 6 months. Design: Subjects will be enrolled into this single center Phase 1/1b study following the specific or their respective diseases. In Phase 1 part of the study, two dose levels, 720 microgram/kg and 960 microgram/kg, will be compared. Six subjects will be enrolled in each dose level, and a single dose of NT-I7 will be delivered intramuscularly. The purpose of this part of the study is to select the OBD. OBD is defined as the dose that yields the greatest rise in peak absolute total T-cell counts (peak value at any timepoint during the first 28 days post NT-I7 administration) with corresponding rise in naive subsets of CD4+ and CD8+ T cells without accompanying substantial toxicities. Absolute increase is a delta between the baseline counts and the peak counts within each subject. -Once OBD is determined, the Phase 1b portion of this study will begin. Subjects will undergo immunizations with various antigens, randomized to be administered either before or after a single dose of NT-I7 at OBD. This inter-subject randomization of the order in which the immunizations are administered (according to the Sequence 1 or to the Sequence 2 schedule) will allow all immunocompromised subjects entered on the Phase 1b portion of the study to receive NT-I7. The vaccines, randomly assigned to be administered before NT-I7 therapy are administered six weeks before the administration of NT-I7 therapy. The vaccines, randomly assigned to be administered after NT-I7 therapy are administered 3 weeks after NT-I7 injection.

Tracking Information