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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00150878
• Other study ID #: 9005-2003
• Status: Terminated
• Phase: Phase 3
• First received: September 6, 2005
• Last updated: June 19, 2013
• Start date: December 2003
• Est. completion date: December 2010

Study information

• Verified date: June 2013
• Source: University Hospital Carl Gustav Carus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 198
• Est. completion date: December 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Other:
• Conditioning therapy
Preparation before allogeneic transplantation

Locations

Country	Name	City	State
Germany	Medizinische Klinik und Poliklinik I	Dresden

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Carl Gustav Carus

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Stelljes M, Bornhauser M, Kroger M, Beyer J, Sauerland MC, Heinecke A, Berning B, Scheffold C, Silling G, Buchner T, Neubauer A, Fauser AA, Ehninger G, Berdel WE, Kienast J; Cooperative German Transplant Study Group. Conditioning with 8-Gy total body irradiation and fludarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia. Blood. 2005 Nov 1;106(9):3314-21. Epub 2005 Jul 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-related mortality at 12 months after transplantation	Proportion of patients dying without prior relapse	12 months	Yes
Secondary	Disease-free and Overall survival	Proportion of patients alive without relapse	5 years	No
Secondary	Grade 3-4 extramedullary toxicity	Percentage of patients with grade II-IV acute GvHD	100 days	Yes

External Links

•   Central Leukemia Study Group