Clinical trial NCT02707393: Allogeneic Stem Cell Transplantation for Children With CML
Official title: Allogeneic Stem Cell Transplantation for Children and Adolescents With CML: Conditioning Regimen, Donor Selection, Supportive Care and Diagnostic Procedures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Chronic Myeloid Leukemia
Keywords: stem cell transplantation
pediatrics
Lead sponsor: St. Anna Kinderkrebsforschung
Sponsor class: OTHER
First posted: 2016-03-14
Enrollment: 13
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: transplant related mortality
timeFrame: one year
Secondary outcomes:
measure: overall survival
timeFrame: five years
measure: event free survival
timeFrame: five years
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Universitätsklinik für Kinder- und Jugendheilkunde
city: Wien
country: Austria
facility: St. Anna Kinderspital
city: Praha
country: Czechia
facility: Hospital Motol, Department of Pediatric Hematology and Oncology, BMT Unit
city: Monza
country: Italy
facility: Clinica Pediatrica
Study officials:
affiliation: St. Anna Kinderspital
name: Susanne Matthes, MD
role: STUDY_CHAIR
References: