ALL-SCT BFM International- HSCT in Children and Adolescents With ALL

Study Overview
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Brief Summary
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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
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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.

Official Title
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Allogeneic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia

Conditions
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Lymphoblastic Leukemia, Acute, Childhood;

Intervention / Treatment
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* Drug: VP16
* Radiation: TBI
* Drug: VP16, ATG
* Radiation: TBI
* Drug: Fludarabine, OKT3, Treosulfan, Thiotepa
* Drug: VP16, ATG
* Radiation: TBI


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: MSD - Matched Sibling Donor<br>patients with a MSD receive a conditioning of TBI (12 Gy, 6 fractions) and VP16 60mg/kg for one day (-3) | Drug: VP16<br>* patients with MSD receive as conditioning VP16 60mg/kg/d on day -3<br>* Other names: Etoposid;Radiation: TBI<br>* patients with a MSD receive TBI (12Gy in 6 fractions) as conditioning<br>* Other names: Total body irradiation;|
| Other: MD - Matched Donor<br>patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive TBI (12Gy in 6 fractions), VP16 60mg/kg/d on day -3 and ATG fresenius 20mg/kg/d on day -3,-2,-1 | Drug: VP16, ATG<br>* 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<br>* Other names: Etoposid, Antithymoglobuline;Radiation: TBI<br>* patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive TBI (12Gy in 6 fractions)<br>* Other names: total body irradiation;|
| Other: MMD - Mismatched Donor<br>Patients with a MMD 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 | Drug: Fludarabine, OKT3, Treosulfan, Thiotepa<br>* 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<br>* Other names: ATG: Antithymoglobuline;Drug: VP16, ATG<br>* patients with MMD-transplantation (8/10)receive VP16 60mg/kg/d on day -4, ATG from day -3 to day-1 20mg/kg/d<br>* Other names: ATG: Antithymoglobuline;Radiation: TBI<br>* patients with a MMD-transplantation (8/10) receive 12 Gy in 6 fractions<br>* Other names: TBI: total body irradiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event free survival | Event-free and overall survival after allogeneic HSCT | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patients with GvHD acute and chronic Graft-versus-Host-Disease (GvHD) | 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 | 10 years | 
| occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT | evaluation of organ dysfunctions according to WHO Toxicity score | 10 years | 
| occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT | evaluation of growth retardation and endocrine dysfunction | 10 years | 
| occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT | Evaluation of incidence of aseptic bone necrosis. | 10 years | 
| occurrence and course of subsequent malignancies after chemotherapy with subsequent allogeneic HSCT | Evaluation of incidence of secondary cancer after total body irradiation and/or chemotherapy | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALL, HSCT, children, adolescents