Format

Send to

Choose Destination
Ann Oncol. 2015 Jul;26(7):1353-62. doi: 10.1093/annonc/mdv173. Epub 2015 Apr 7.

ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer patients.

Author information

1
Department of Medical Oncology, Leon Berard Cancer Center, Lyon Lyon University, Lyon ISPB, Lyon 1 University, Lyon CNRS UMR5286, Cancer Research Center of Lyon, Lyon.
2
Lyon University, Lyon ISPB, Lyon 1 University, Lyon CNRS UMR5286, Cancer Research Center of Lyon, Lyon Innovation in Immuno-monitoring and Immunotherapy Platform (P3I), Leon Berard Cancer Center Team 11, INSERM U1052, Cancer Research Center of Lyon, Lyon.
3
Department of Medical Oncology, Leon Berard Cancer Center, Lyon Lyon University, Lyon ISPB, Lyon 1 University, Lyon CNRS UMR5286, Cancer Research Center of Lyon, Lyon isabelle.ray-coquard@lyon.unicancer.fr.
4
Clinical Research Platform (DRCI), Leon Berard Cancer Center, Lyon.
5
Innovation in Immuno-monitoring and Immunotherapy Platform (P3I), Leon Berard Cancer Center.
6
Department of Medical Oncology, Leon Berard Cancer Center, Lyon.
7
Cytheris SA, Issy-Les-Moulineaux.
8
Biological Sample Management Platform (BB-0033-00050).
9
Pharmacy, Leon Berard Cancer Center, Lyon.
10
Revimmune, Paris, France.
11
Department of Medical Oncology, Leon Berard Cancer Center, Lyon Lyon University, Lyon ISPB, Lyon 1 University, Lyon CNRS UMR5286, Cancer Research Center of Lyon, Lyon Team 11, INSERM U1052, Cancer Research Center of Lyon, Lyon.

Abstract

BACKGROUND:

Lymphopenia is a predictive factor for hematological toxicity, progression and early death in advanced cancers including metastatic breast cancer (MBC). CYT107 is a recombinant interleukin 7 (IL-7) (Cytheris, now Revimmune), well tolerated and able to expand lymphocyte pool in humans. The aims of this study were to determine the optimal schedule to deliver CYT107 and to assess its effect on clinical end points.

PATIENT AND METHODS:

This placebo-controlled, double blind, phase IIa was conducted in MBC patients with <1500/µl lymphocytes treated with capecitabine. Using a 2-by-2 factorial design, 20 patients were randomly allocated to four arms to receive (i) before chemotherapy: CYT107 or placebo; then (ii) during chemotherapy: CYT107 or placebo. The primary end point was CD4+ count changes before and during chemotherapy. Secondary end points were hematological toxicity, safety, overall response, progression-free survival (PFS) and overall survival (OS). Quantification and functional competence of circulating immune cells were also assessed.

RESULTS:

When administered before chemotherapy, CYT107 induced a significant increase of CD4+ [+148.1% in CYT107 versus +9.9% in placebo groups, (Wilcoxon, P = 0.002)] and CD8+ T-cell counts, including both naïve and memory subsets. When CYT107 was administered during chemotherapy, the magnitude of CD4+ and CD8+ increase was less important. No modulation of immune cell functional competence was observed. CYT107 was well tolerated with no related ≥grade 3 adverse events except 1 fatal suspected unexpected serious adverse reaction (SUSAR) of uncertain relationship. Of the 12 cases evaluable for response, 6 of 7 patients (86%) receiving CYT107 before chemotherapy achieved a response or stabilization, whereas two of five patients (40%) receiving placebo achieved the same result. No significant difference was observed for PFS or OS.

CONCLUSION:

In lymphopenic MBC, CYT107 increases CD4+ and other T-cell subset counts without altering their function. A larger clinical trial to demonstrate its impact on clinical outcome is warranted.

CLINICALTRIALSGOV IDENTIFIER:

NCT01362107.

KEYWORDS:

immune reconstitution; interleukin 7; lymphopenia; metastatic breast cancer

PMID:
25851629
DOI:
10.1093/annonc/mdv173
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center