Allogeneic Stem Cell Transplantation for Children With CML

April 14, 2021 updated by: St. Anna Kinderkrebsforschung

Allogeneic Stem Cell Transplantation for Children and Adolescents With CML: Conditioning Regimen, Donor Selection, Supportive Care and Diagnostic Procedures

In children and adolescents with chronic myeloid leukaemia (CML) stem cell transplantation (SCT) may be a valid alternative to the life-long treatment with tyrosinkinase inhibitors (TKI). This trial aims to evaluate the use of a reduced intensity conditioning regimen (RIC), consisting of fludarabine, melphalan and thiotepa in order to minimize transplant related mortality and toxic late effects. Strict post-transplant monitoring and reintroduction of TKI as well as donor lymphocyte infusions (DLI) in case of relevant residual disease are part of the protocol.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Chronic myeloid leukaemia (CML) is a rare disease in children with an incidence of 3-5% of all paediatric leukaemias. Since the introduction of tyrosinkinase inhibitors (TKI) stem cell transplantation (SCT) is no longer the first choice treatment for patients with early phase CML.

However life-long treatment with TKI may not be feasable in several cases due to side effects such as growth retardation, non-compliance and resistance. This protocol evaluates the feasibility of SCT following a reduced intensity conditioning regimen (RIC) consisting of fludarabine, melphalan, thiotepa and thymoglobuline (ATG). Matched siblings and matched unrelated donors are permitted for stem cell donation. In case of unrelated donors tissue typing has to be done by high resolution molecular typing. Donors with 10/10 or 9/10 identical allels in the human leukocyte antigen (HLA) system are accepted. Preferred stem cell source is bone marrow but peripheral blood stem cells and umbilical cord blood are also allowed. Graft-versus-Host-Disease (GvHD)-prophylaxis is achieved with cyclosporine A and mycophenolate mofetil.

Monitoring of the breakpoint cluster region - Abelson (BCR/ABL) rearrangement is performed monthly in the first year after SCT. In case of BCR/ABL positivity TKI are given in the first year after SCT. Followed by donor lymphocyte infusions (DLI) later on if BCR/ABL positivity persists.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz, Austria, 8036
        • Universitätsklinik für Kinder- und Jugendheilkunde
      • Wien, Austria, 1050
        • St. Anna Kinderspital
  • Czechia
      • Praha, Czechia, 15006
        • Hospital Motol, Department of Pediatric Hematology and Oncology, BMT Unit
  • Italy
      • Monza, Italy, 20052
        • Clinica Pediatrica

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • children and adolescents with BCR/ABL positive CML in chronic phase, who are eligible for allogeneic stem cell transplantation, irrespective of the previous treatment strategy
  • availability of a HLA matched sibling donor (MSD), a matched family donor, a matched unrelated donor or a matched unrelated cord blood (MD)
  • informed consent

Exclusion Criteria:

  • unavailability of MSD or MD
  • patients in accelerated phase or blast crisis
  • pregnancy
  • previous autologous or allogeneic SCT
  • no informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: single arm
Fludarabine intravenous - daily dose: 40mg/sqm on day -7, -6, -5, -4; Thiotepa intravenous - daily dose: 2 x 5mg/kg on day -3; Melphalan intravenous - daily dose: 140/mg/sqm on day - 2; ATG intravenous - dose according to local standards on day -3, -2, -1; bone marrow or peripheral blood stem cells of an HLA identical sibling or matched unrelated donor on day 0; GvHD propyhlaxis with Mycophenolate Mofetil and Cyclosporine A
Drug: Fludarabine
infusion
Other Names:
  • Fludara
Drug: Thiotepa
infusion
Other Names:
  • TESPA
  • Thioplex
Drug: Melphalan
infusion
Other Names:
  • Alkeran
Drug: ATG
infusion
Other Names:
  • Thymoglobulin
Drug: Cyclosporine A
infusion, orally if possible
Other Names:
  • Sandimmune
Drug: Mycophenolate mofetil
infusion
Other Names:
  • CellCept
Biological: bone marrow or peripheral blood stem cells
infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
transplant related mortality
Time Frame: one year
one year

Secondary Outcome Measures

Outcome Measure
Time Frame
overall survival
Time Frame: five years
five years
event free survival
Time Frame: five years
five years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Anna Kinderkrebsforschung

Investigators

  • Study Chair: Susanne Matthes, MD, St. Anna Kinderspital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 30, 2009

Primary Completion (Actual)

December 1, 2020

Study Completion (Actual)

December 1, 2020

Study Registration Dates

First Submitted

March 1, 2016

First Submitted That Met QC Criteria

March 11, 2016

First Posted (Estimate)

March 14, 2016

Study Record Updates

Last Update Posted (Actual)

April 15, 2021

Last Update Submitted That Met QC Criteria

April 14, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EudraCT 2008-000569-50

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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