Allogeneic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia
Trial Snapshot
- Phase
- Phase 3
- Enrollment
- 400
- Locations
- 24
- Primary Endpoint
- Event-free and overall survival after allogeneic haematopoietic stem cell transplantation (HSCT)
Study Overview
Brief Summary
With this protocol the ALL-SZT BFM international study group wants
to evaluate whether hematopoietic stem cell transplantation (HSCT) from matched family or unrelated matched donors (MD) is equivalent to the HSCT from matched sibling donors (MSD).
to evaluate the efficacy of haematopoietic stem cell transplantation (HSCT) from mismatched family or unrelated mismatched donors (MMD) as compared to HSCT from matched sibling donor (MSD) and matched donor (MD).
to determine whether therapy has been carried out according to the main haematopoietic stem cell transplantation (HSCT) protocol recommendations. The standardisation of the treatment options during haematopoietic stem cell transplantation (HSCT) from different donor types aims at the achievement of an optimal comparison of survival after HSCT with survival after chemotherapy only.
to prospectively evaluate and compare the incidence of acute and chronic graft- versus-host-disease (GvHD) after haematopoietic stem cell transplantation (HSCT) from matched sibling donor (MSD), from matched donor (MD) and from mismatched donor (MMD).
Detailed Description
Patients with high risk or relapsed acute lymphoblastic leukaemia (ALL) have a worse prognosis compared to all other patients with ALL. For these patients additional therapy approaches are required after they have achieved remission with multimodal chemotherapy. Allogeneic haematopoetic stem cell transplantation shows promising results mainly due to an immunological antileukaemic control by the graft-versus-leukaemia effect, but treatment related mortality and morbidity remains a serious problem.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 3 Months to 18 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •age at time of initial diagnosis or relapse diagnosis, respectively under or equal 18 years
- •indication for allogeneic hematopoietic stem cell transplantation (HSCT)
- •complete remission before hematopoietic stem cell transplantation (HSCT)
- •written consent of the parents (legal guardian) and, if necessary, the minor patient via Informed Consent Form
- •no pregnancy
- •no secondary malignancy
- •no previous hematopoietic stem cell transplantation (HSCT)
- •hematopoietic stem cell transplantation (HSCT) is performed in a study participating centre.
Exclusion Criteria
- •age at time of initial diagnosis or relapse diagnosis, respectively above 18 years
- •no indication for allogeneic HSCT
- •no complete remission before SCT
- •no written consent of the parents (legal guardian) and, if necessary, the minor patient via Informed Consent Form
- •pregnancy
- •secondary malignancy
- •previous HSCT
- •HSCT is not performed in a study participating centre.
Arms & Interventions
MD - matched donor
patients with a HLA (Human Leukocyte Antigen) matched unrelated Donor (9/10 oder 10/10) receive total body irradiation (TBI) (12Gy in 6 fractions), VP16 60mg/kg/d on day -3 and ATG fresenius 20mg/kg/d on day -3,-2,-1
Intervention: TBI (Radiation)
MSD - matched sibling donor
patients with a MSD receive a conditioning of total body irradiation (TBI) (12 Gy, 6 fractions) and VP16 60mg/kg for one day (-3)
Intervention: TBI (Radiation)
MD - matched donor
patients with a HLA (Human Leukocyte Antigen) matched unrelated Donor (9/10 oder 10/10) receive total body irradiation (TBI) (12Gy in 6 fractions), VP16 60mg/kg/d on day -3 and ATG fresenius 20mg/kg/d on day -3,-2,-1
Intervention: VP16, ATG (Drug)
MMD - mismatched Donor
Patients with a mismatched donor receive stem cells either from cord blood, a haploidentical donor (parent) or from a non-related donor with a match less or equal 8/10
Intervention: Fludarabine, OKT3, Treosulfan, Thiotepa (Drug)
MMD - mismatched Donor
Patients with a mismatched donor receive stem cells either from cord blood, a haploidentical donor (parent) or from a non-related donor with a match less or equal 8/10
Intervention: VP16, ATG (Drug)
MMD - mismatched Donor
Patients with a mismatched donor receive stem cells either from cord blood, a haploidentical donor (parent) or from a non-related donor with a match less or equal 8/10
Intervention: TBI (Radiation)
MSD - matched sibling donor
patients with a MSD receive a conditioning of total body irradiation (TBI) (12 Gy, 6 fractions) and VP16 60mg/kg for one day (-3)
Intervention: VP16 (Drug)
Outcomes
Primary Outcomes
Event-free and overall survival after allogeneic haematopoietic stem cell transplantation (HSCT)
Time Frame: 14 years
Secondary Outcomes
- occurrence of acute and chronic Graft-versus-Host-Disease (GvHD)(14 years)
- occurrence and course of late effects after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)(14 years)
- occurrence and course of secondary malignancies after chemotherapy with subsequent allogeneic hematopoietic stem cell transplantation (HSCT)(14 years)
Investigators
Prof. Christina Peters
MD, PHD
St. Anna Kinderspital, Austria