Micro-transplantation in Elderly Patients With Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This study aims at evaluating the safety and the tolerance of the micro-transplantation in elderly patients with acute myeloid leukemia who are ineligible to conventional allogeneic transplantation.

Detailed Description
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Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with a median age at diagnosis of 65 years. Outcomes of AML in elderly population remain unsatisfactory with low rates of complete remission, poor disease-free and overall survival. Therapeutic management of older patients with AML deals with patient-related features (i.e. comorbid conditions and performance status) as well as disease-related prognostic factors (i.e. cytogenetics and molecular genetics). Even if allogeneic hematopoietic-cell transplantation provides the strongest antineoplasic effect, this treatment option remains limited for older patients owing to toxicities, the development of significant graft-versus-host disease (GVHD) and logistics of donor availability. More recently, micro-transplantation has emerged as an alternative strategy based on the infusion of mobilized HLA-mismatched related donor cells after induction chemotherapy, thus exerting a graft-versus-leukemia effect without substantial donor engraftment and GVHD. Therefore, there is much of interest in investigating the efficacy and the safety of this method for older patients with AML who are not candidates for allogeneic stem cell transplantation.

Official Title
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A Phase II, Multicenter, Open Label Study Evaluating the Efficacy and the Tolerance of Micro-transplantation in Elderly Patients With Acute Myeloid Leukemia (MTSA)

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Other: HLA-mismatched micro-transplantation after induction chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient affiliated to a social security regimen or beneficiary of the same Signed written informed consent form Patient, ≥ 60 years-old - < 75 years-old, with established diagnosis of de novo or secondary AML with intermediate-risk or adverse-risk cytogenetic profile, or with established myelodysplasic syndromes (RAEB), in pathologically confirmed complete remission following anti-leukemic induction therapy (<5% blasts) Contra-indication to conditioning regimen in conventional allogeneic transplantation Exclusion Criteria: Patient with established diagnosis of acute myeloid leukemia with standard-risk cytogenetic profile Promyelocytic leukemia t(15;17) CBF-AML t(8;21) or inv(16) Normal karyotype with a favorable molecular profile: NPM1+ and FLT3-; NPM1+, FLT3- and double mutation CEBPα or chronic myeloid leukemia in blastic phase Patient under guardianship or deprived of his liberty or any condition that may affect the patient's ability to understand and sign the informed consent Refusing participation

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 75 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: HLA-mismatched micro-transplantation<br>HLA-mismatched micro-transplantation | Other: HLA-mismatched micro-transplantation after induction chemotherapy<br>* HLA-mismatched micro-transplantation after induction chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of overall survival | Rate of overall survival will be reported. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematopoietic recovery | Number of platelets will be reported. | 3 months | 
| Hematopoietic recovery | Number of neutrophils will be reported. | 3 months | 
| Hematopoietic recovery | Percentage of leukaemic blasts will be reported. | 3 months | 
| Rate of complete remission | Rate of complete remission : | 2 years | 
| GVHD (graft versus host disease) | Presence of graft versus host disease will be reported. | 2 years | 
| Median overall survival | Median overall survival will be calculated. | 2 years | 
| Median progression-free survival | Median progression-free survival will be calculated. | 2 years | 
| Microchimerism | Presence of microchimerism will be reported. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Elderly, Acute Myeloid Leukemia, Micro-transplantation, Graft-versus-leukemia