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

This study has been terminated.
(Insurance coverage reached)
Sponsor:
Information provided by:
University Hospital Carl Gustav Carus
ClinicalTrials.gov Identifier:
NCT00150878
First received: September 6, 2005
Last updated: June 19, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Other: Conditioning therapy
Phase 3

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

Resource links provided by NLM:


Further study details as provided by University Hospital Carl Gustav Carus:

Primary Outcome Measures:
  • Treatment-related mortality at 12 months after transplantation [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Proportion of patients dying without prior relapse


Secondary Outcome Measures:
  • Disease-free and Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Proportion of patients alive without relapse

  • Grade 3-4 extramedullary toxicity [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    Percentage of patients with grade II-IV acute GvHD


Enrollment: 198
Study Start Date: December 2003
Study Completion Date: December 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00150878

Locations
Germany
Medizinische Klinik und Poliklinik I
Dresden, Germany, 01307
Sponsors and Collaborators
University Hospital Carl Gustav Carus
Investigators
Study Director: Gerhard Ehninger, MD Director of Med. Klink und Poliklinik I, Technical University Dresden
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital Dresden
ClinicalTrials.gov Identifier: NCT00150878     History of Changes
Other Study ID Numbers: 9005-2003
Study First Received: September 6, 2005
Last Updated: June 19, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Carl Gustav Carus:
Reduced-intensity conditioning
Fludarabine
Acute myeloid Leukemia
Treatment-related mortality

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on September 22, 2014