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

Phase 3

Terminated

• Conditions: Acute Myeloid Leukemia
• Interventions: Other: Conditioning therapy

• Registration Number: NCT00150878
• Lead Sponsor: University Hospital Carl Gustav Carus

Brief Summary

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

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

Study Timeline

• Study Start: 2003-12
• Study First Submitted: 2005-09-06
• Study First Submitted QC: 2005-09-06
• Study First Posted: 2005-09-08
• Primary Completion: 2009-12
• Study Completion: 2010-12
• Status Verified: 2013-06
• Last Update Submitted: 2013-06-19
• Last Update Posted: 2013-06-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 198

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
12 Gy/Cyclophosphamide	Conditioning therapy	Standard intensity conditioning
8 Gy /Fludarabine	Conditioning therapy	Reduced-intensity conditioning

Primary Outcome Measures

Name	Time	Method
Treatment-related mortality at 12 months after transplantation	12 months	Proportion of patients dying without prior relapse

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Medizinische Klinik und Poliklinik I; 🇩🇪 Dresden, Germany