Acute Myeloid LeukemiaPhase 3NCT00150878
Standard vs. Reduced-Intensity Conditioning in Patients With Acute Myeloid Leukemia in First Remission
A Phase 3 study testing Conditioning therapy in people with Acute Myeloid Leukemia, run by University Hospital Carl Gustav Carus at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Conditioning therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 198 participants
- Where
- 1 siteGermany
- Study dates
- Dec 2003to Dec 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 9Show fewer
- Contraindications to receive prescribed study medication
- HIV infection
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Conditioning therapy
- Keywords
- Reduced-intensity conditioning, Fludarabine, Acute myeloid Leukemia, Treatment-related mortality
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conditioning therapyOther
Preparation before allogeneic transplantation
| Study group | Role | What they receive |
|---|---|---|
| 12 Gy/Cyclophosphamide | Other | Standard intensity conditioning Receives: Other: Conditioning therapy |
| 8 Gy /Fludarabine | Experimental | Reduced-intensity conditioning Receives: Other: Conditioning therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-related mortality at 12 months after transplantation
Proportion of patients dying without prior relapse
Measured: 12 months
Secondary outcomes (2)
Disease-free and Overall survival
Proportion of patients alive without relapse
Measured: 5 years
Grade 3-4 extramedullary toxicity
Percentage of patients with grade II-IV acute GvHD
Measured: 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2005 (estimated)
- Study startDec 2003
- Primary completionDec 2009
- Study completionDec 2010
Why it stopped: Insurance coverage reached
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 198 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Carl Gustav Carus
- Sponsor type
- University, hospital or other
- Investigators
- Gerhard Ehninger, MD, Study director, Director of Med. Klink und Poliklinik I, Technical University Dresden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00150878
- Sponsor's protocol ID
- 9005-2003
- Status last verified
- Jun 2013
- First submitted
- 6 Sep 2005
- Last updated
- 20 Jun 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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. doi: 10.1182/blood-2005-04-1377. Epub 2005 Jul 14.
PubMed 16020510Fasslrinner F, Schetelig J, Burchert A, Kramer M, Trenschel R, Hegenbart U, Stadler M, Schafer-Eckart K, Batzel M, Eich H, Stuschke M, Engenhart-Cabillic R, Krause M, Dreger P, Neubauer A, Ehninger G, Beelen D, Berdel WE, Siepmann T, Stelljes M, Bornhauser M. Long-term efficacy of reduced-intensity versus myeloablative conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: retrospective follow-up of an open-label, randomised phase 3 trial. Lancet Haematol. 2018 Apr;5(4):e161-e169. doi: 10.1016/S2352-3026(18)30022-X. Epub 2018 Mar 14.
PubMed 29550384Bornhauser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schafer-Eckart K, Holler E, Kroger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. doi: 10.1016/S1470-2045(12)70349-2. Epub 2012 Sep 7.
PubMed 22959335
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00150878
- Acronym / sponsor ID
- 9005-2003
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Reduced-intensity conditioning, Fludarabine, Acute myeloid Leukemia, Treatment-related mortality
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insurance coverage reached
- Enrolment
- 198 participants (actual)
- Lead sponsor
- University Hospital Carl Gustav CarusUniversity, hospital or other
- Study start
- Dec 2003
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 8 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 12 Gy/Cyclophosphamide | Other | Other: Conditioning therapyStandard intensity conditioning |
| 8 Gy /Fludarabine | Experimental | Other: Conditioning therapyReduced-intensity conditioning |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Conditioning therapyPreparation before allogeneic transplantation | Other | 12 Gy/Cyclophosphamide, 8 Gy /Fludarabine |
Primary outcome
Treatment-related mortality at 12 months after transplantation
Time frame: 12 months
Proportion of patients dying without prior relapse
2 secondary outcomes
Disease-free and Overall survival
Time frame: 5 years
Grade 3-4 extramedullary toxicity
Time frame: 100 days
Results and safety
The study was stopped early (reason given: Insurance coverage reached). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2013.
- Background: PubMed 16020510Stelljes 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. doi: 10.1182/blood-2005-04-1377. Epub 2005 Jul 14.
- Derived from this study: PubMed 29550384Fasslrinner F, Schetelig J, Burchert A, Kramer M, Trenschel R, Hegenbart U, Stadler M, Schafer-Eckart K, Batzel M, Eich H, Stuschke M, Engenhart-Cabillic R, Krause M, Dreger P, Neubauer A, Ehninger G, Beelen D, Berdel WE, Siepmann T, Stelljes M, Bornhauser M. Long-term efficacy of reduced-intensity versus myeloablative conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: retrospective follow-up of an open-label, randomised phase 3 trial. Lancet Haematol. 2018 Apr;5(4):e161-e169. doi: 10.1016/S2352-3026(18)30022-X. Epub 2018 Mar 14.
- Derived from this study: PubMed 22959335Bornhauser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M, Baurmann H, Schafer-Eckart K, Holler E, Kroger N, Schmid C, Einsele H, Kiehl MG, Hiddemann W, Schwerdtfeger R, Buchholz S, Dreger P, Neubauer A, Berdel WE, Ehninger G, Beelen DW, Schetelig J, Stelljes M. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012 Oct;13(10):1035-44. doi: 10.1016/S1470-2045(12)70349-2. Epub 2012 Sep 7.
- Central Leukemia Study GroupLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerhard Ehninger, MD study director
Director of Med. Klink und Poliklinik I, Technical University Dresden
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Conditioning therapy in people with Acute Myeloid Leukemia, run by University Hospital Carl Gustav Carus at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Insurance coverage reached). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-related mortality at 12 months after transplantation (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00150878, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2013.