Allogeneic Stem Cell Transplantation for Children With CML

Sponsor

St. Anna Kinderkrebsforschung (Other)

Overall Status

Completed

CT.gov ID

NCT02707393

Collaborator

(none)

Enrollment

Locations

Arm

139.1

Actual Duration (Months)

3.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia	Drug: Fludarabine Drug: Thiotepa Drug: Melphalan Drug: ATG Drug: Cyclosporine A Drug: Mycophenolate mofetil Biological: bone marrow or peripheral blood stem cells	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 30, 2009

Actual Primary Completion Date :

Dec 1, 2020

Actual Study Completion Date :

Dec 1, 2020

Arms and Interventions

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: Thioplex TESPA 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

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:

Thioplex

TESPA

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

Outcome Measures

Primary Outcome Measures

transplant related mortality [one year]

Secondary Outcome Measures

overall survival [five years]
event free survival [five years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Universitätsklinik für Kinder- und Jugendheilkunde	Graz	Austria	8036
2	St. Anna Kinderspital	Wien	Austria	1050
3	Hospital Motol, Department of Pediatric Hematology and Oncology, BMT Unit	Praha	Czechia	15006
4	Clinica Pediatrica	Monza	Italy	20052