Allogeneic Stem Cell Transplantation for Children With CML

NCT ID: NCT02707393

Last Updated: 2021-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2020-12-01

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.

Conditions

Chronic Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

infusion

Thiotepa

Intervention Type: DRUG

infusion

Melphalan

Intervention Type: DRUG

infusion

ATG

Intervention Type: DRUG

infusion

Cyclosporine A

Intervention Type: DRUG

infusion, orally if possible

Mycophenolate mofetil

Intervention Type: DRUG

infusion

bone marrow or peripheral blood stem cells

Intervention Type: BIOLOGICAL

infusion

Interventions

Fludarabine

infusion

Intervention Type: DRUG

Thiotepa

infusion

Intervention Type: DRUG

Melphalan

infusion

Intervention Type: DRUG

ATG

infusion

Intervention Type: DRUG

Cyclosporine A

infusion, orally if possible

Intervention Type: DRUG

Mycophenolate mofetil

infusion

Intervention Type: DRUG

bone marrow or peripheral blood stem cells

infusion

Intervention Type: BIOLOGICAL

Other Intervention Names

Fludara; Thioplex; TESPA; Alkeran; Thymoglobulin; Sandimmune; CellCept

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Anna Kinderkrebsforschung

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susanne Matthes, MD

Role: STUDY_CHAIR

St. Anna Kinderspital

Locations

Universitätsklinik für Kinder- und Jugendheilkunde

Graz, , Austria

St. Anna Kinderspital

Vienna, , Austria

Hospital Motol, Department of Pediatric Hematology and Oncology, BMT Unit

Prague, , Czechia

Clinica Pediatrica

Monza, , Italy

Countries

Austria; Czechia; Italy

Other Identifiers

EudraCT 2008-000569-50

Identifier Type: -

Identifier Source: org_study_id