Lymphoblastic Leukemia, Acute, Childhood;
Conditions
Keywords
ALL, HSCT, children, adolescents
Brief summary
With this protocol the ALL-SCT BFM international study group wants * to evaluate whether hematopoietic stem cell transplantation (HSCT) from matched family or unrelated donors (MD) is equivalent to the HSCT from matched sibling donors (MSD). * to evaluate the efficacy of hematopoietic stem cell transplantation (HSCT)from mismatched family or unrelated donors (MMD) as compared to HSCT from matched sibling donors or matched donors. * to determine whether therapy has been carried out according to the main HSCT protocol recommendations. The standardisation of the treatment options during 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 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.
Interventions
DRUGVP16
patients with MSD receive as conditioning VP16 60mg/kg/d on day -3
RADIATIONTBI
patients with a MSD receive TBI (12Gy in 6 fractions) as conditioning
DRUGVP16, ATG
patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive VP16 60mg/kg/d on day -3 and ATG fresenius 20mg/kg/d on day -3,-2,-1
patients with a MMD (haploidentical or cord blood) receive Fludarabine 30mg/m²/d on day -9 to -5, ATG fresenius 20mg/kg/d on day -3,-2,-1, Treosulfan 14g/m²/d on day -7 to -5 and Thiotepa 2x5mg/kg/d on day -4
Sponsors
St. Anna Kinderkrebsforschung
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 18 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event free survival | 10 years | Event-free and overall survival after allogeneic HSCT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| number of patients with GvHD acute and chronic Graft-versus-Host-Disease (GvHD) | 10 years | evaluation of the incidence and severity of acute Grade I-IV graft versus Host disease and of limited or extensive chronic graft versus host disease |
| occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT | 10 years | evaluation of organ dysfunctions according to WHO Toxicity score |
| occurrence and course of subsequent malignancies after chemotherapy with subsequent allogeneic HSCT | 10 years | Evaluation of incidence of secondary cancer after total body irradiation and/or chemotherapy |
Countries
Austria, Czechia, Denmark, France, Israel, Italy, Netherlands, Poland, Slovakia, Sweden, Turkey (Türkiye)
Outcome results
None listed