Clinical Trial: Study Evaluating Impact of IL-7 on CD4 Lymphopenia, Risks of Severe Haematological Toxicity and Tumor Progression in Metastatic Breast Cancer Patients

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomised, Multicentric, Phase 2a Study Evaluating the Impact of an Immunotherapy by IL-7 on CD4 Lymphopenia, Risks of Severe Haematological Toxicity and Tumor Progress

Brief Summary:

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.


Detailed Summary:

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).

Sponsor: Centre Leon Berard

Current Primary Outcome: to determine the optimal schedule to deliver CYT107 during chemotherapy based on restoration of CD4 count [ Time Frame: after 11 weeks of treatment ]

Evolution of CD4 count from Day 0 to Week 11 with repeated measures from D0 to W12 (D0, D21, D57, D78).


Original Primary Outcome: to determine the optimal schedule to deliver CYT107 during chemotherapy based on restoration of CD4 count [ Time Frame: after 12 weeks of treatment ]

Evolution of CD4 count from Day 0 to Week 12 with repeated measures from D0 to W12 (D0, D21, D63, D84).


Current Secondary Outcome:

  • 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 Frame: at the end of study (M12) ]
    Time from randomisation to first evidence of progression or death of any cause.
  • To assess the impact of CYT107 on compliance to chemotherapy regimen (dose intensity, number of chemotherapy cycles). [ Time Frame: at the end of study (M12) ]
    Number of CT cycles, CT dose delays and/or reduction, CT discontinuation
  • To assess the impact of CYT107 on CD4 lymphopenia over the study period [ Time Frame: at the end of study (M12) ]
    Evolution of CD4 count from Day 0 to end of study visit
  • 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) [ Time Frame: D0, D21, D57, D78 and at end of study M12 ]
    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).
  • to evaluate if CYT107 treatment will selectively improve the functional response of T cells, DC subsets and NK cells [ Time Frame: D0, D21, D57, D78 and at the end of study M12 ]
    Analysis of the functional response of T cells, DC subsets and NK cells
  • 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) [ Time Frame: D0, D21, D57, D78 and at the end of study M12 ]
    • 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.
  • to evaluate if CYT107 treatment will enable to increase TCR diversity (analysis of combinatorial diversity). [ Time Frame: D0, D21, D57, D78 and at the end of study M12 ]
    Evaluation of T cell receptor diversity using ImmuneTraCkeR test and Constel'ID software (ImmunID Technologies, Grenoble, France).
  • To assess the impact of CYT107 treatment on overall incidence of side effects [ Time Frame: after 12 weeks of treatment ]
    Number of patients with AEs (any type any grade) using NCI-CTCAE scale (version 4.0) from D0 to W12


Original Secondary Outcome:

  • 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 Frame: at the end of study (M12) ]
    Time from randomisation to first evidence of progression or death of any cause.
  • To assess the impact of CYT107 on compliance to chemotherapy regimen (dose intensity, number of chemotherapy cycles). [ Time Frame: at the end of study (M12) ]
    Number of CT cycles, CT dose delays and/or reduction, CT discontinuation
  • To assess the impact of CYT107 on CD4 lymphopenia over the study period [ Time Frame: at the end of study (M12) ]
    Evolution of CD4 count from Day 0 to end of study visit
  • 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) [ Time Frame: D0, D21, D63, D184 and at end of study M12 ]
    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).
  • to evaluate if CYT107 treatment will selectively improve the functional response of T cells, DC subsets and NK cells [ Time Frame: D0, D21, D63, D184 and at the end of study M12 ]
    Analysis of the functional response of T cells, DC subsets and NK cells
  • 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) [ Time Frame: D0, D21, D63, D184 and at the end of study M12 ]
    • 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.
  • to evaluate if CYT107 treatment will enable to increase TCR diversity (analysis of combinatorial diversity). [ Time Frame: D0, D21, D63, D184 and at the end of study M12 ]
    Evaluation of T cell receptor diversity using ImmuneTraCkeR test and Constel'ID software (ImmunID Technologies, Grenoble, France).
  • To assess the impact of CYT107 treatment on overall incidence of side effects [ Time Frame: after 12 weeks of treatment ]
    Number of patients with AEs (any type any grade) using NCI-CTCAE scale (version 4.0) from D0 to W12


Information By: Centre Leon Berard

Dates:
Date Received: June 6, 2011
Date Started: June 2011
Date Completion:
Last Updated: February 6, 2015
Last Verified: December 2013