Phase 3 Trial for AML Patients in CR2 Comparing 8Gy TBI /Fludarabine to Conditioning With TBI 12Gy/Cyclophosphamide

Study Overview
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Brief Summary
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For patients with acute myeloid leukemia (AML), allogeneic hematopoetic stem cell transplantation (HSCT) is one of the most potent treatment options currently available. In order to overcome the high risk of fatal treatment-related complications, reduced intensity and nonmyeloablative conditioning regimens for allogeneic HSCT are currently being explored in various hematological malignancies including AML. At least for allogeneic HSCT in AML, the optimal dose-intensity of preparative regimens for disease control at an acceptable rate of treatment-related lethal complications has not been determined. The investigators, therefore, evaluated reduced intensity myeloablative conditioning with 8 Gy TBI and fludarabine in AML patients considered ineligible for conventional conditioning in a phase 2 trial (data published in BLOOD by Stelljes et al., 2005). The results suggest that with 8 Gy TBI/fludarabine, conditioning related and unrelated donor transplants can be performed in AML patients in first or second complete remission (CR) with a remarkably low 2-year non relapse mortality (NRM) and satisfactory disease control. Based on these data a randomized phase 3 trial for patients with AML in CR≥2 is currently being conducted by the Cooperative German Transplant Study Group comparing TBI 8 Gy/fludarabine to conventionally dosed conditioning with TBI 12 Gy/cyclophosphamide.

Official Title
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Randomized Phase 3 Trial for Patients With AML in CR2 Comparing Total Body Irradiation (TBI) With 8Gy/Fludarabine to Conditioning With TBI 12Gy/Cyclophosphamide

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Procedure: conditioning for allogeneic HSCT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with AML in second complete remission HLA-identical related (HLA * A, B, and DR) or HLA-compatible unrelated donor with maximum of one Ag mismatch Ages 18-60 years Written informed consent from the patient Written informed consent from the donor No major organ dysfunction Exclusion Criteria: Cardiac failure (New York Heart Association [NYHA] grade II-IV) Renal failure (creatinine > 2.0 mg/dl) Hepatic failure (total bilirubin > 3 mg/dl) Severe neurological/psychiatric disorder Previous allogeneic HSCT Contra-indications for used drugs HIV infection Non-compliance to processing of personal data according to the protocol

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: conditioning therapy with 12 Gy TBI / cyclophosphamide 120<br> | Procedure: conditioning for allogeneic HSCT<br> <br> |
| Experimental: conditioning therapy with 8 Gy TBI / fludarabine 120<br> | Procedure: conditioning for allogeneic HSCT<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| treatment related mortality |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| event free survival |  |  | 
| overall survival |  |  | 
| cumulative incidence of acute and chronic graft-versus-host disease (GvHD) |  |  | 
| activity index (ECOG) |  |  | 
| organ function |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, allogeneic HSCT, reduced intensity conditioning, randomized trail