Clinical trial NCT01368107: Study Evaluating Impact of IL-7 on CD4 Lymphopenia, Risks of Severe Haematological Toxicity and Tumor Progression in Metastatic Breast Cancer Patients
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 Progression in Metastatic Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Keywords: IL-7
metastatic breast cancer patients
lymphopenia
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: Cytheris, Inc.
First posted: 2011-06-07
Enrollment: 24
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 description: 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).

Eligibility criteria: Inclusion Criteria:

* Female aged more than 18 years
* Histologic diagnosis of metastatic breast cancer to be treated with capecitabine at study entry. NB: Patients previously treated with capecitabine are eligible only if more than 6 months have elapsed since the last capecitabine intake.
* Lymphopenic (i.e. with at least one value of lymphocyte count 1500/µL within 15 days before Day 0).
* Performance status ECOG of 0, 1,2 or 3
* Life expectancy ≥ 6months
* Adequate bone marrow, hepatic and renal function as follows:

  * Neutrophils ≥ 1,000/µL
  * Platelets ≥ 100 109/µL
  * ASAT, ALAT, or Alkaline Phosphatase ≤ 2.5 x ULN
  * Total Bilirubin ≤ 1.5 x ULN
  * INR ≤ 1.5
  * Calculated creatinin clearance ≥ 60mL/min (Cockcroft formula or MDRD formula for patients older than 65 years old)- Ability to understand and sign informed consent
* Covered by a medical insurance.

Exclusion Criteria:

* Prior history of other malignancies other than breast cancer (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the subjects has been free of the disease for at least 3 years.
* No resolution of specific toxicities related to any prior anti-cancer therapy to Grade ≤2 according to the NCI CTCAE v.4.0 (except lymphopenia, alopecia and neuropathy)
* Wash out period of less than 5 times the half-life of previous anti-cancer treatment before study entry, except if previous chemotherapy treatment before study entry. NB: For patient previously treated by hormonotherapy, a wash out period of 1 week will be sufficient
* Uncontrolled hypertension (i.e., resting systolic blood pressure greater than140 mmHg or resting diastolic blood pressure greater than 90 mmHg), despite pharmacologic antihypertensive treatment, confirmed with a second blood pressure measurement done later in the same day
* History of lymphoid malignancy (e.g. Hodgkin disease, non Hodgkin lymphoma, Leukemia).
* History of splenectomy or hematologic disease associated with hypersplenism, such as gamma or beta-thalassemia, hereditary spherocytosis, Gaucher's disease, or autoimmune hemolytic anemia.
* Any cardiac, pulmonary, thyroid, renal, hepatic, neurological severe/uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
* Any history of severe auto-immune disease
* Hepatitis B antigen (HBs Ag) positive, Hepatitis C (HCV Ab) antibody positive or HCV RNA detectable
* Documented HIV-1 positivity
* History of cardiovascular disorders grade \>2 (NYHA) within 6 months preceding the inclusion
* Active uncontrolled viral, fungal or bacterial infection
* Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements (participants must agree to refrain from substance abuse use during the entire course of the study)
* Pregnant or breast-feeding women
* No use of effective birth control methods for women of childbearing potential
* Any contraindications to capecitabine treatment (refer to Xeloda SPC Appendix 11) and to any other anti-cancer treatment authorized as per protocol (refer to respective SPC for specific contraindications)

Primary outcomes:
measure: to determine the optimal schedule to deliver CYT107 during chemotherapy based on restoration of CD4 count
timeFrame: after 11 weeks of treatment
Secondary outcomes:
measure: to determine if CYT107 treatment enables to reduce the incidence of severe haematological toxicity (any type of haematological toxicity Grade ≥ 3) post-chemotherapy
timeFrame: at the end of study M12
measure: To assess the impact of CYT107 on progression-free survival
timeFrame: at the end of study (M12)
measure: To assess the impact of CYT107 on compliance to chemotherapy regimen (dose intensity, number of chemotherapy cycles).
timeFrame: at the end of study (M12)
measure: To assess the impact of CYT107 on CD4 lymphopenia over the study period
timeFrame: at the end of study (M12)
measure: 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)
timeFrame: D0, D21, D57, D78 and at end of study M12
measure: to evaluate if CYT107 treatment will selectively improve the functional response of T cells, DC subsets and NK cells
timeFrame: D0, D21, D57, D78 and at the end of study M12
measure: 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)
timeFrame: D0, D21, D57, D78 and at the end of study M12
measure: to evaluate if CYT107 treatment will enable to increase TCR diversity (analysis of combinatorial diversity).
timeFrame: D0, D21, D57, D78 and at the end of study M12
measure: To assess the impact of CYT107 treatment on overall incidence of side effects
timeFrame: after 12 weeks of treatment
Other outcomes:
Locations:
city: Lyon
country: France
facility: Centre Leon Berard
city: Paris
country: France
facility: Institut Curie
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre Léon Bérard, Lyon
name: Isabelle Ray Coquart
role: PRINCIPAL_INVESTIGATOR
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