Standard vs. Reduced-Intensity Conditioning in Patients With Acute Myeloid Leukemia in First Remission
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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 |
- Treatment-related mortality at 12 months after transplantation [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Proportion of patients dying without prior relapse
- 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 |
| Estimated Study Completion Date: | July 2011 |
| 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 |
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| Germany | |
| Medizinische Klinik und Poliklinik I | |
| Dresden, Germany, 01307 | |
| 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: | May 6, 2011 |
| 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 Leukemia, Myeloid, Acute Leukemia, Myeloid Neoplasms by Histologic Type Neoplasms Cyclophosphamide Fludarabine monophosphate 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 May 19, 2013