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

NCT01368107 | Completed Phase 2 DMC

• 2 other identifiers: ELYPSE 72011-000226-30
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

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.

Conditions

Metastatic Breast Cancer

Keywords

IL-7; metastatic breast cancer patients; lymphopenia

Outcome Measures

Primary Outcomes (1)

• 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).

  after 11 weeks of treatment

Secondary Outcomes (9)

• to determine if CYT107 treatment enables to reduce the incidence of severe haematological toxicity (any type of haematological toxicity Grade ≥ 3) post-chemotherapy

  at the end of study M12

• To assess the impact of CYT107 on progression-free survival

  at the end of study (M12)

• To assess the impact of CYT107 on compliance to chemotherapy regimen (dose intensity, number of chemotherapy cycles).

  at the end of study (M12)

• To assess the impact of CYT107 on CD4 lymphopenia over the study period

  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)

  D0, D21, D57, D78 and at end of study M12

Study Arms (4)

Placebo Arm

PLACEBO COMPARATOR

the patients will receive Placebo before the 1st and during the 3rd CT cycle (N=6)

Drug: placebo

CYT107 treatment before CT

EXPERIMENTAL

patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle and the placebo during the 3rd CT cycle (N=6)

Drug: placebo; Drug: interleukin 7

CYT107 treatment during CT

EXPERIMENTAL

patients will receive the placebo before the 1st CT cycle and a delayed treatment with CYT107 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (N=6)

Drug: interleukin 7

CYT107 treatment before and during CT

EXPERIMENTAL

patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle and a maintenance cycle of IL-7 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (N=6).

Drug: interleukin 7

Interventions

placebo DRUG

Placebo before the 1st (D0, D7, D14)and during the 3rd CT cycle (D57, D64, D71)

CYT107 treatment before CT; Placebo Arm

interleukin 7 DRUG

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)

CYT107 treatment before CT

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Centre Leon Berard: lead
• Ministry of Health, France: collaborator
• Cytheris, Inc.: collaborator

Study Sites (3)

Centre Leon Berard

Lyon, France

Location

Institut Curie

Paris, 75005, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Related Publications (30)

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  RESULT

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MeSH Terms

Conditions

Breast Neoplasms; Lymphopenia

Interventions

Interleukin-7

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Isabelle Ray Coquart

  Centre Léon Bérard, Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2011
• First Posted: June 7, 2011
• Study Start: June 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: June 1, 2014
• Last Updated: February 9, 2015

Record last verified: 2013-12

Locations

FR (3)