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

June 19, 2013 updated by: University Hospital Carl Gustav Carus

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

198

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Dresden, Germany, 01307
        • Medizinische Klinik und Poliklinik I

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Carl Gustav Carus

Investigators

  • Study Director: Gerhard Ehninger, MD, Director of Med. Klink und Poliklinik I, Technical University Dresden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2003

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

September 6, 2005

First Submitted That Met QC Criteria

September 6, 2005

First Posted (Estimate)

September 8, 2005

Study Record Updates

Last Update Posted (Estimate)

June 20, 2013

Last Update Submitted That Met QC Criteria

June 19, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9005-2003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Myeloid Leukemia

Clinical Trials on Conditioning therapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Liberia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe