Allogeneic Stem Cell Transplantation for Children With CML

Chronic Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02707393
• Other study ID #: EudraCT 2008-000569-50
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: April 30, 2009
• Est. completion date: December 1, 2020

Study information

• Verified date: April 2021
• Source: St. Anna Kinderkrebsforschung
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: December 1, 2020
• Est. primary completion date: December 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Intervention

Drug:
• Fludarabine
infusion
• Thiotepa
infusion
• Melphalan
infusion
• ATG
infusion
• Cyclosporine A
infusion, orally if possible
• Mycophenolate mofetil
infusion

Biological:
• bone marrow or peripheral blood stem cells
infusion

Locations

Country	Name	City	State
Austria	Universitätsklinik für Kinder- und Jugendheilkunde	Graz
Austria	St. Anna Kinderspital	Wien
Czechia	Hospital Motol, Department of Pediatric Hematology and Oncology, BMT Unit	Praha
Italy	Clinica Pediatrica	Monza

Sponsors (1)

Lead Sponsor	Collaborator
St. Anna Kinderkrebsforschung

Countries where clinical trial is conducted

Austria,  Czechia,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	transplant related mortality		one year
Secondary	overall survival		five years
Secondary	event free survival		five years