NCT02670564

Brief 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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
1,000

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Apr 2013

Longer than P75 for phase_4

Geographic Reach
1 country

4 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2013

Completed
2.3 years until next milestone

First Submitted

Initial submission to the registry

July 3, 2015

Completed
7 months until next milestone

First Posted

Study publicly available on registry

February 2, 2016

Completed
5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2021

Completed
5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2026

Completed
Last Updated

April 16, 2019

Status Verified

April 1, 2019

Enrollment Period

8 years

First QC Date

July 3, 2015

Last Update Submit

April 15, 2019

Conditions

Keywords

pharmacogeneticsbusulfantreosulfanhematopoietic stem cell transplantationfludarabinepediatric patientsTBIleukemialeukemia, lymphoidprecursor cell lymphoblastic Leukemia-LymphomaImmune System diseaseImmunoproliferative Disordersstem cell transplantationchildren and adolescenthigh risk acute lymphoblastic leukemiaNCT01949129 add-onALL SCTped FORUM

Outcome Measures

Primary Outcomes (1)

  • Genetic variants in participants as a marker of risk of Adverse events and/or Efficacy of the studied agents

    Genotyping of candidates genes related to pharmacokinetics and pharmacodynamics of the studied agents. Association study between the herein genetic variants and the below mentioned phenotypes (odd ratio).

    through study completion, an average of 2 years

Secondary Outcomes (10)

  • Number of participants with acute Graft-versus-host disease (aGvHD) according to the Glucksberg scale and Seattle criteria

    18 months after inclusion of first patient, afterwards, annually up to 10 years

  • Number of participants with chronic Graft-versus-host disease (cGvHD) according to the Glucksberg scale and Seattle criteria

    18 months after inclusion of first patient, afterwards, annually up to 10 years

  • Number of participants with VOD/SOS according to the Seattle criteria

    18 months after inclusion of first patient, afterwards, annually up to 10 years

  • Number of participants with Neutrophil recovery as a measure of Safety and Tolerability

    18 months after inclusion of first patient, afterwards, annually up to 10 years

  • Number of participants with Platelet recovery as a measure of Safety and Tolerability

    18 months after inclusion of first patient, afterwards, annually up to 10 years

  • +5 more secondary outcomes

Other Outcomes (8)

  • Administered Bu dose(mg) per day

    Measures assessed at time of conditioning (up to 5days)

  • Target Bu plasma concentration(ng/ml)

    Measures assessed at time of conditioning (up to 5days)

  • Target Bu Area under the plasma concentration versus time curve (AUC) (min*ng/ml)

    Measures assessed at time of conditioning (up to 5days)

  • +5 more other outcomes

Study Arms (3)

Total body irradiation (TBI)

EXPERIMENTAL

The Pharmacogenomics add-on requires 2X 5ml blood EDTA for further DNA analyses. Note this is an add-on study to NCT 01949129, THE ALL SCTped FORUM study. Please refer to the main study for further details.

Genetic: Pharmacogenomics

Busulfan

EXPERIMENTAL

The Pharmacogenomics add-on requires 2X 5ml blood EDTA for further DNA analyses. Note this is an add-on study to NCT 01949129, THE ALL SCTped FORUM study. Please refer to the main study for further details.

Genetic: PharmacogenomicsOther: Busulfan plasma level measurements

Treosulfan

EXPERIMENTAL

The Pharmacogenomics add-on requires 2X 5ml blood EDTA for further DNA analyses. Note this is an add-on study to NCT 01949129, THE ALL SCTped FORUM study. Please refer to the main study for further details.

Genetic: Pharmacogenomics

Interventions

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.

Also known as: DNA analyses
BusulfanTotal body irradiation (TBI)Treosulfan

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

Busulfan

Eligibility Criteria

AgeUp to 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Hôpital Cantonal de Genève, Département de Pédiatrie

Geneva, Cansearch Laboratory, 1211, Switzerland

RECRUITING

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

Basel, 4056, Switzerland

RECRUITING

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

Geneva, 1211, Switzerland

RECRUITING

Universitäts-Kinderspital

Zurich, 8032, Switzerland

RECRUITING

Related Links

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-LymphomaLeukemiaLeukemia, LymphoidImmune System DiseasesImmunoproliferative Disorders

Interventions

Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic Diseases

Intervention Hierarchy (Ancestors)

Genetic TestingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisInvestigative TechniquesGenetic TechniquesGenetic ServicesHealth ServicesHealth Care Facilities Workforce and ServicesDiagnostic ServicesPreventive Health Services

Study Officials

  • Christina Peters, Prof. MD PhD

    St. Anna Kinderspital, Vienna, Austria

    STUDY CHAIR
  • Peter Bader, Prof. MD PhD

    Klinik für Kinder- u. Jugendheilkunde III, Johann Wolfgang Goethe Universität, Frankfurt, Germany

    STUDY CHAIR
  • Franco Locatelli, Prof. MD PhD

    Department of Pediatric Hematology and Oncology IRCCS Ospedale, Rome, Italy

    STUDY CHAIR
  • Marc Ansari, MD, PD

    Département de Pédiatrie, Hôpital Cantonal de Genève

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Marc Ansari, MD, PD

CONTACT

Patricia Huezo-Diaz Curtis, PhD

CONTACT

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 3, 2015

First Posted

February 2, 2016

Study Start

April 1, 2013

Primary Completion

April 1, 2021

Study Completion

April 1, 2026

Last Updated

April 16, 2019

Record last verified: 2019-04

Locations