Date: 2011-05-11
Type of information:
phase: 2a
Announcement: initiation
Company: Cytheris (France) Centre Léon Bérard (France) ImmunID (France)
Product: combination regimen of IL-7 (CYT107) and Xeloda® (capecitabine)
Action mechanism: Recombinant human interleukin-7 (CYT107) is a critical immune-modulator for immune T-cell.
Disease: metastatic breast cancer
Therapeutic area: Cancer - Oncology
Country: France
Trial
details: ELYPSE-7 is a randomised, monocentric, double-blind Phase IIa study evaluating the impact of IL-7 immunotherapy on CD4 lymphopenia and TCR repertoire diversity, risks of severe haematological toxicity and tumor progression in metastatic breast cancer patients. Twenty-four patients will be enrolled at a single center (Centre Léon Bérard, Lyon, France) where the study is under the direction of Isabelle Ray-Coquard, MD, PhD, Principal Investigator.
The duration of the investigation for each patient will include a study drug treatment period of at least 12 weeks (including 3 x 3-week cycles of chemotherapy) and a follow-up period for a maximum of one year (or until disease progression).
Chemotherapy will be extended until disease progression, unacceptable toxicity, or willingness to stop. The inclusion period is expected to be six months with the treatment period and follow-up lasting up to one year.
All patients will receive standard anti-cancer therapy prescribed for second line metastatic breast cancer patients: Xeloda® (capecitabine) at an oral dose of 2500mg/day for 14 days over a 21-day cycle period. In addition, all patients will be randomly allocated in a factorial design to one of the following four study arms:
• Arm 1: (Placebo Group) Patients will receive Placebo before the start of chemotherapy (at D0, D7 and D14) and during the 3rd cycle of chemotherapy (D63, D70 and D77).
• Arm 2: (Pre-IL-7 Treatment Group) Patients will receive CYT107 (one subcutaneous injection at 10 ?g/kg/week for three weeks) before the 1st cycle of chemotherapy (at D0, D7 and D14) and will receive the placebo during the 3rd cycle of chemotherapy (D63, D70 and D77).
• Arm 3: (Concomitant IL-7 Treatment Group) Patients will receive Placebo before the 1st cycle of chemotherapy (D0, D7 and D14) and will receive CYT107 (one subcutaneous injection at 10 microg/kg/week for three weeks) during the 3rd cycle of chemotherapy (at D63, D70 and D77).
• Arm 4: (Pre- and Concomitant IL-7 Treatment) Patients will receive CYT107 (one subcutaneous injection at 10 microg/kg/week for three weeks) before the 1st cycle of chemotherapy (D0, D7 and D14) and again (one subcutaneous injection at 10 µg/kg/week for three weeks) during the 3rd cycle of chemotherapy (D63, D70 and D77).
The primary endpoint of the study is the evolution of patient CD4 counts from D0 to W12 with repeated measures at D0, W3, W9, and W12. This will help in defining the optimal schedule of CYT107 administration during chemotherapy, based on the restoration of patient CD4 counts.
Secondary endpoints include the impact of CYT107 treatment on the incidence of severe hematological toxicity as indicated by the number of patients experiencing any type of hematological Adverse Event (including anemia, thrombopenia, lymphopenia, or neutropenia) of Grade more than 3 from D0 to W12. At this stage, the quality of T cell repertoire diversity reconstitution will also be assessed.
Latest
news: Cytheris, the Centre Léon Bérard (Lyon) and ImmunID Technologies have announced initiation of a Phase IIa clinical trial that will evaluate multiple combinations of recombinant human interleukin-7 (CYT107), the investigational multifunctional cytokine under development by Cytheris, and a chemotherapeutic agent, XELODA® (capecitabine, Roche/Genentech), in the treatment of metastatic breast cancer.
The trial is designed to explore the optimal schedule for delivery of CYT107 during standard capecitabine chemotherapy, with the aim of immune reconstitution and collection of preliminary data on the impact of CYT107 on severe hematological toxicity and tumor progression in second line metastatic breast cancer patients. The immunorestorative properties of IL7, which include its ability to provide T cells to attack any residual disease, are expected to have a significant impact on survival in this patient population, where a low CD4 T cell count associated with poor receptor diversity detected before initiation of chemotherapy is a known predictive factor indicating overall survival of less than 6 months compared to almost two years for non-lymphopenic patients.
Conducted as a collaborative effort of the Centre Léon Bérard (the study sponsor), ImmunID Technologies, and Cytheris, the study, known as ELYPSE-7, is designed to evaluate whether CYT107 treatment is able to correct lymphopenia postchemotherapy in advanced cancer patients and whether the correction of this lymphopenia by restoration of the immune system will result in a broadening of the repertoire of T cells and a reduction in the risk of severe haematological toxicity, tumor progression and early death.
