RecruitingPhase 4NCT02670564

ALL SCTped FORUM - Pharmacogenomic Study (add-on Study)

Allogeneic Stem Cell Transplant for Children and Adolescents With Acute Lymoblastic Leukemia FORUM - Pharmacogenomic Study (add-on Study)


Sponsor

Swiss Pediatric Oncology Group

Enrollment

1,000 participants

Start Date

Apr 1, 2013

Study Type

INTERVENTIONAL

Conditions

Summary

Pharmacogenomics (PG) offers the opportunity to individualize treatment according to patient genetic variations which influence activity of enzyme metabolizing or acting in the pathway of prescribed chemotherapy drugs. This add-on research aims to prospectively investigate variations in several candidate genes related to all types of chemotherapeutic drugs and TBI used in the main related study NCT 01949129, THE ALL SCTped FORUM study for their potential role as predictive biomarkers of PK variability and outcome of myeloablative therapy for pediatric patients receiving an allogeneic hematopoietic stem cell transplantation in acute lymphoblastic leukemia.


Eligibility

Max Age: 18 Years

Inclusion Criteria16

  • Note this is an add-on study to NCT 01949129, THE ALL SCTped FORUM study. Please refer to the main study for further details.
  • Gender
  • Both: both female and male participants are being studied
  • Age Limits
  • Minimum Age: N/A
  • Maximum Age: age at time of screening less than 18 years old
  • Accepts Healthy Volunteers: no
  • Eligibility Criteria
  • Patients with ALL (except for patients with B-ALL)
  • indication for allogeneic HSCT
  • complete remission (CR) before HSCT
  • written consent of the parents (legal guardian) and, if necessary, the minor patient via "Informed Consent Form"
  • no pregnancy
  • no secondary malignancy
  • no previous HSCT
  • HSCT is performed in a study participating centre

Exclusion Criteria9

  • Non Hodgkin-Lymphoma
  • ALL with extramedullary involvement with indication for TBI
  • CNS involvement at the timepoint of screening
  • Trisomy 21
  • The whole protocol or essential parts are declined either by patient himself/herself or the respective legal guardian
  • No consent is given for saving and propagation of anonymous medical data for study reasons
  • Severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion (e.g. malformation syndromes, cardiac malformations, metabolic disorders)
  • Karnofsky / Lansky score \< 50%
  • Subjects unwilling or unable to comply with the study procedures

Interventions

GENETICPharmacogenomics

Blood samples (2x5ml EDTA tubes) should be collected just before the start of the conditioning regimen from every patient regardless of therapeutic arm by every centre and stored ≤-20°C Patient should be in remission (MRD negative) for this sampling, otherwise the sample should be taken using a mouth swab/saliva (not intravenously). For second transplant patients, please provide DNA taken before first transplant or a fresh saliva samples.

OTHERBusulfan plasma level measurements

Bu PK analysis after the first dose of IV Bu (+potential subsequent ones). Blood sampling: -\>For Bu 4 X/d: Before the first Bu dose (Time 0), then straight after the end of infusion (Time 1), then at 15 min (Time 2), 30 min (Time 3), 1 hour (Time 4) and 4 hour (Time 5) after the end of infusion -\>For Bu 1 X/d: Before the first Bu dose (Time 0), then straight after the end of infusion (Time 1), then at 1 hour (Time 2), 3 hour (Time 3), 5 hour (Time 4), 7 hour (Time 5) and 11 hour (Time 6) after the end of infusion. For centers not performing BU TDM, perform Dried Blood Sampling (DBS) analysis: -\> 0.5ml blood sample should be collected and 5µl spotted onto DBS cards in duplicate. Dry them max 5 hours and then keep in a sealed envelope and store at -80°C, as below


Locations(4)

Hôpital Cantonal de Genève, Département de Pédiatrie

Geneva, Cansearch Laboratory, Switzerland

Universitäts-Kinderspital beider Basel (UKBB), Onkologie/Hämatologie

Basel, Switzerland

HUG Hôpitaux Universitaire de Genève, Unité d'onco-hématologie pédiatrique

Geneva, Switzerland

Universitäts-Kinderspital

Zurich, Switzerland

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NCT02670564


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