Allogenic Stem Cell Transplantation for Children, Adolescents and Young Adults With Relapsed or Refractory AML

Study Overview
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Brief Summary
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To evaluate whether stem cell transplantation from a matched sibling donor is equivalent to a matched unrelated donor in in a second complete remission of acute myeloid leukemia (AML). To evaluate whether stem cell transplantation (SCT) after chemotherapy (FLAMSA-schema) increases survival compared to a threshold derived from historical data To evaluate whether SCT from haploidentical donors for children having no matched donor will result in better survival with acceptable toxicity.

Detailed Description
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Target variables: Treatment response Event Free Survival Leukemia Free Survival Graft Versus Host Disease Regimen related toxicity

Official Title
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Allogenic Stem Cell Transplantation for Children, Adolescents and Young Adults With Relapsed or Refractory AML; Multi Center Therapy Concept

Conditions
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Acute Myeloid Leukemia (AML)

Intervention / Treatment
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* Biological: Hematopoietic stem cells from bone marrow or peripheral blood


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 0-21 years Patients suffering from either refractory de novo AML or relapsed AML or patients with very high risk AML in CR1 In sexually active patients two reliable contraception methods are used. This includes every combination of a hormonal contraceptive (such as injection, transdermal patch, implant, cervical ring) or of an intrauterine device(IUD) with a barrier method (e.g. diaphragm, cervical cap, or condom) or with a spermicide. Written informed consent of patient, parents or legal guardians Exclusion Criteria: Severe renal impairment (GFR < 30% predicted for age) Pregnant or lactating females Current participation in another clinical trial Patients ≥ 12 years old for Group 1 (BuCyMel) (patients younger that 12 years continue to be included)

Ages Eligible for Study
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Maximum Age: 21 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Group I: Relapsed AML-patients with blast cell reduction to <20% before the second course of induction therapy. These patients will receive conventional SCT. Group II: Patients with non response to frontline treatment of AML, patients with blast cells <20% before the second course of induction therapy who do not achieve a second remission and relapsed AML-patients with blast cells >=20% before the second course of induction therapy. If these patients have a matched donor (MSD/MD) they will receive SCT with FLAMSA. Group III: Patients who are eligible for Group II but have no matched donor. These patients will receive SCT from a haploidentical donor. | Biological: Hematopoietic stem cells from bone marrow or peripheral blood<br>* > = 2 x 10*8 nucleated cells (WBC)/kg body weight of the recipient or rather > = 4 x 10*6 nucleated CD34+ cells / kg body weight are required for engraftment. Suspension of stem cells is administered via intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate whether stem cell transplantation (SCT) from a matched sibling donor (MSD) is equivalent to a matched unrelated donor (MUD) in second complete remission (CR2). |  | day 100 | 
| To evaluate whether FLAMSA increases leukemia free survival (LFS) and overall survival (OS) as compared to a historic control group |  | day 100 | 
| To evaluate whether SCT from haploidentical donors for children having no matched donor will result in an acceptable toxicity profile and a better LFS as compared to historic controls. |  | day 100 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prospective evaluation of event free survival (EFS), LFS, and OS after SCT from either a MSD or a MUD |  | day 100 | 
| To evaluate whether it is feasible to standardize transplantation procedures in children with AML within the AML-Berlin/Frankfurt/Münster (BFM) study network |  | day 100 | 
| Decrease of transplantation associated mortality by standardized donor selection criteria |  | day 100 | 
| To further evaluate the contribution of immunomediated effects for the treatment of children suffering from very high risk AML |  | day 100 | 
| Prospective evaluation of late toxicities |  | day 100 and year 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapsed or refractory AML, in children, adolescents and young adults