Standard vs. Reduced-Intensity Conditioning in Patients With Acute Myeloid Leukemia in First Remission

Study Overview
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Brief Summary
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The primary goal of the study is to show that the treatment-related mortality of allogeneic hematopoietic stem cell transplantation an be significantly reduced by using a combination of 8 Gy total-body-irradiation and fludarabine in comparison to the conventional combination of 12 Gy TBI and 120 mg/kg Cyclophosphamide.

Detailed Description
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Transplant-related deaths because of extramedullary toxicity and graft-versus host disease remain the major causes for treatment-failure in patients with AMl receiving allogeneic hematopoietic stem cell transplantation. In phase II study, M . Stelljes and coworkers could show, that a reduced dose of total-body- irradiation and fludarabine can be safely used in patients with AML at various disease stages. The best results could be achieved in patients who had been in complete remission by the time of inclusion. Therefore this prospective trial was initiated to compare the new conditioning regimen with the standard regimen of 12 Gy TBI/Cyclophosphamide 120 mg/kg in patients ith AML in first remission. After having achieved complete remission, and giving informed consent, patients are stratified according to marrow cytogenetics, age and type of induction therapy and subsequently randomized to receive on of the mentioned conditioning therapies. The primary end-point will be non-relapse mortality. The hypothesis would be, that the one-year mortality can be reduced from 25 to 15%. Given a power of 0.8 and a first-error of 5%, 252 patients will have to be randomized. Secondary endpoints include: 3 year overall-and disease-free survival Rate of grade II-IV acute GvHD Rate of grade 3-4 extramedullary toxicity

Official Title
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Randomized Phase III Comparison of 12 Gy TBI and Cyclophosphamide 120 mg/kg With Fludarabine 120 mg/Sqm and 8 Gy TBI Before Allogeneic Transplantation in Patients With Acute Myeloid Leukemia in First Remission

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Other: Conditioning therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of acute myeloid leukemia in first remission Standard-or high-risk marrow cytogenetics HLA-matched related or unrelated donor available (in case of high-risk disease) Age 18 to 60 Informed consent Consent of donor to donate peripheral blood stem cells sufficient liver function (elevation of transferases < 2.5 x upper limit) Exclusion Criteria: AML with t(5;17) AML with t((8;21) clinically relevant heart failure (NYHA II-IV) Renal failure (creatinine > 200 µg/ml) Liver function failure (bilirubin > 3 mg/dl) Concomitant Neurological or psychiatric disease Contraindications to receive prescribed study medication HIV infection Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 12 Gy/Cyclophosphamide<br>Standard intensity conditioning | Other: Conditioning therapy<br>* Preparation before allogeneic transplantation<br>|
| Experimental: 8 Gy /Fludarabine<br>Reduced-intensity conditioning | Other: Conditioning therapy<br>* Preparation before allogeneic transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related mortality at 12 months after transplantation | Proportion of patients dying without prior relapse | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free and Overall survival | Proportion of patients alive without relapse | 5 years | 
| Grade 3-4 extramedullary toxicity | Percentage of patients with grade II-IV acute GvHD | 100 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Reduced-intensity conditioning, Fludarabine, Acute myeloid Leukemia, Treatment-related mortality