Dependence Receptors and Leukemia

Dependence Receptors in Childhood Acute Leukemia

Acute leukaemias (AL) are the first cause of cancer in children, with a majority of B acute lymphoblastic leukemia (ALL). Some of the processes causing leukemogenesis are already identified and well characterized in some AL subtypes such as translocation t (12; 21) of good prognosis in ALL. However, translocations are not sufficient to explain all the different processes of leukemogenesis, and other processes such as genetic / epigenetic mutations leading to oncogene activation / inhibition of tumor suppressor genes are the object research. Among the latter, mutations in tumor suppressor genes such as DCC (Deleted in Colorectal Cancer) have recently been identified in solid cancers, such as in hemopathies. This gene was subsequently characterized as encoding a "dependence receptor" specifically binding to its Netrin-1 ligand.

Dependence receptors (RDs) are transmembrane receptors that cause cell death in the absence of their ligand. RD decreases tumor progression and overexpression of their ligands is observed in many cancers, such as B lymphomatous hemopathies in adults. Inhibition of the RD-ligand interaction constitutes a new and original therapeutic target in oncology.

The aim of this study is to investigate whether RDs, in particular DCC, are expressed in acute leukemia cells at the time of diagnosis or relapse in patients aged 1 to 18 years, and then in these patients at the time of the remission balance. This research will be both qualitative and quantitative.

Study Overview

• Status: Unknown
• Conditions: Acute Lymphoblastic Leukemia; Acute Leukemia
• Intervention / Treatment: Genetic: Genetic analyses

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: Carine HALFON-DOMENECH, M.D, PhD; Phone Number: +33 04 69 16 65 67; Email: carine.halfon-domenech@chu-lyon.fr
• Study Contact Backup: Name: Patrick MEHLEN, MD; Phone Number: +33 04-78-78-28-70; Email: patrick.mehlen@lyon.unicancer.fr

Study Locations

• France
  • Lyon, France, 69008
    • Institut D'Hematologie Et D'Oncologie Pediatrique
    • Contact: Carine HALFON-DOMENECH, M.D, PhD; Phone Number: +33 04 69 16 65 67; Email: carine.halfon-domenech@chu-lyon.fr
    • Contact: Patrick MEHLEN, MD; Phone Number: 04-78-78-28-70; Email: patrick.mehlen@lyon.unicancer.fr
    • Principal Investigator: Carine HALFON-DOMENECH, M.D, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The target population consists of patients aged 1 to 18 years treated at the Institute of Hematology and Pediatric Oncology (IHOPe), a department of Prof. Y. Bertrand, for acute leukemia (LA) at the time of diagnosis initial, or relapse, after obtaining signed parental consent. The same patients will benefit from a new sample at the time of their remission balance.

Description

Inclusion Criteria:

• aged between 1 and 18 years
• taken care of at the Institute of Hematology and Pediatric Oncology (Service of Professor Yves Bertrand, IHOPe)
• for acute lymphoblastic or myeloblastic leukemia
• initial diagnosis or relapse
• who do not have a vital emergency criterion at the time of taking care (see exclusion criteria)
• affiliated to a social security scheme (100% assumed)
• after signing the informed consent of the holders of parental authority

Exclusion Criteria:

• less than 1 year, or more than 18 years to diagnosis
• with chronic leukemia
• severe anemia at diagnosis (hemoglobin <40g / l), or a state of shock whatever the cause (infectious, cardiogenic, hypovolemic)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Pediatric acute leukemia; Patients of the Institute of Hematology and Pediatric Oncology (IHOPe) with acute leukemia (LA) who came for initial diagnosis, relapse, or at the time of their remission .

Genetic: Genetic analyses; Patients treated at the Institute of Hematology and Pediatric Oncology (IHOPe), a department of Prof. Y. Bertrand, for acute leukemia (LA) at the time of diagnosis initial, or relapse, after obtaining signed parental consent. The same patients will benefit from a new sample at the time of their remission balance. Analyses for this research will be made from bone marrow aspiration samples performed for diagnosis and treatment of these patients. The medical team will investigate whether RDs, in particular DCC, are expressed in acute leukemia cells at the time of diagnosis or relapse and then in these patients at the time of the remission balance. This research will be both qualitative and quantitative. Next, investigators will characterize the existence and then the level of expression of the ligand specific for DCC, Netrin-1, in these same leukemic cells, at the time of diagnosis / relapse and remission.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of specific labeling of the DCC-dependent receptor on the surface of leukemic cells	Primary endpoint: presence of specific labeling of the DCC-dependent receptor on the surface of leukemic cells that will be detectable in flow cytometry. This marking will be both qualitative (positive signal = presence of the receptor, absence of signal = absence of the receptor), and quantitative (percentage of expression of the receptor on the surface of the cells).	Maximum 4 months (sampling at the time of diagnosis / relapse and remission)

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2017
• Primary Completion (Anticipated): May 1, 2019
• Study Completion (Anticipated): November 1, 2019

Study Registration Dates

• First Submitted: September 8, 2017
• First Submitted That Met QC Criteria: September 8, 2017
• First Posted (Actual): September 11, 2017

Study Record Updates

• Last Update Posted (Actual): September 12, 2017
• Last Update Submitted That Met QC Criteria: September 11, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: 69HCL16_0806

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No