The purpose of the study is to evaluate the impact of an immunotherapy by IL-7 on CD4 lymphopenia, risks of severe haematological toxicity and tumor progression in metastatic breast cancer patients. The primary objective is to determine the optimal schedule to deliver CYT107 during chemotherapy based on restoration of CD4 count. This study is a phase II, randomised, double-blind, placebo-controlled, single-centre. 24 patients will be included in the study.
A key secondary objective is to determine if CYT107 treatment enables to reduce the incidence of severe haematological toxicity (any type of haematological toxicity Grade ≥ 3) post-chemotherapy. Other secondary objectives are to assess the impact of CYT107 treatment on the following parameters: * Overall incidence of side effects (any type any grade) * Progression-free survival (PFS) * Compliance to chemotherapy regimen (dose intensity, number of chemotherapy cycles). * CD4 lymphopenia over the study period Exploratory biological markers A series of biomarkers analyses will be performed to evaluate if CYT107 treatment will: * selectively stimulate the proliferation and activation of peripheral immune subsets (analysis of phenotype and activation status of peripheral immune e sub-populations) * selectively improve the functional response of T cells, DC subsets and NK cells. * is able to revert tolerogenic immune burden to increase specific anti-tumor response (measure of antigen specific CD8 response, measure of cytokine plasmatic levels) * enable to increase TCR diversity (analysis of combinatorial diversity).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
24
Placebo before the 1st (D0, D7, D14)and during the 3rd CT cycle (D57, D64, D71)
patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle (D0, D7, D14) and the placebo during the 3rd CT cycle (D57, D64, D71)
patients will receive the placebo before the 1st CT cycle (D0, D7, D14) and a delayed treatment with CYT107 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (D57, D64, D71)
patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle (D0, D7, D14) and a maintenance cycle of IL-7 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (D57, D64, D71)
Centre Leon Berard
Lyon, France
Institut Curie
Paris, France
Institut Gustave Roussy
Villejuif, France
to determine the optimal schedule to deliver CYT107 during chemotherapy based on restoration of CD4 count
Evolution of CD4 count from Day 0 to Week 11 with repeated measures from D0 to W12 (D0, D21, D57, D78).
Time frame: after 11 weeks of treatment
to determine if CYT107 treatment enables to reduce the incidence of severe haematological toxicity (any type of haematological toxicity Grade ≥ 3) post-chemotherapy
Time frame: at the end of study M12
To assess the impact of CYT107 on progression-free survival
Time from randomisation to first evidence of progression or death of any cause.
Time frame: at the end of study (M12)
To assess the impact of CYT107 on compliance to chemotherapy regimen (dose intensity, number of chemotherapy cycles).
Number of CT cycles, CT dose delays and/or reduction, CT discontinuation
Time frame: at the end of study (M12)
To assess the impact of CYT107 on CD4 lymphopenia over the study period
Evolution of CD4 count from Day 0 to end of study visit
Time frame: at the end of study (M12)
to evaluate if CYT107 treatment will selectively stimulate the proliferation and activation of peripheral immune subsets (analysis of phenotype and activation status of peripheral immune e sub-populations)
Measure of frequency and activation status of circulating immune subpopulations on fresh whole blood. Multi-parametric marker sets (6-8 markers) will be used to analyse phenotype of immune subpopulations (TCD4+, TCD8+, Treg, T, NK, DC) and their activation status (PD1, ICOS, CD39, CD73, CD62L, CCR7, CD45RO, CD45RA, CD86).
Time frame: D0, D21, D57, D78 and at end of study M12
to evaluate if CYT107 treatment will selectively improve the functional response of T cells, DC subsets and NK cells
Analysis of the functional response of T cells, DC subsets and NK cells
Time frame: D0, D21, D57, D78 and at the end of study M12
to evaluate if CYT107 treatment will is able to revert tolerogenic immune burden to increase specific anti-tumor response (measure of antigen specific CD8 response, measure of cytokine plasmatic levels)
* Analysis of tumor associated antigen (TAA) specific CD8 responses * Quantification of circulating cytokines including mainly, but not limited to, IL-6, IL-2, IFN, VEGF, TNF, IL-15,F FGF using Luminex technology and VEGF, TGF, IL-7R by Elisa.
Time frame: D0, D21, D57, D78 and at the end of study M12
to evaluate if CYT107 treatment will enable to increase TCR diversity (analysis of combinatorial diversity).
Evaluation of T cell receptor diversity using ImmuneTraCkeR test and Constel'ID software (ImmunID Technologies, Grenoble, France).
Time frame: D0, D21, D57, D78 and at the end of study M12
To assess the impact of CYT107 treatment on overall incidence of side effects
Number of patients with AEs (any type any grade) using NCI-CTCAE scale (version 4.0) from D0 to W12
Time frame: after 12 weeks of treatment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.