Acute Myeloid LeukemiaPhase 2NCT00188136
Early Allogeneic Blood Stem Cell Transplantation in High-risk Acute Myeloid Leukemia (AML)
A Phase 2 study testing Melphalan, ATG, Fludarabine in people with Acute Myeloid Leukemia, run by University Hospital Carl Gustav Carus at 1 site in Germany.
Trial summary
Karyotype is a major prognostic risk factor in patients with acute myeloid leukemia (AML) translating into unfavourable outcome in case of poor-risk cytogenetic aberrations. Several studies have shown that allogeneic hematopoietic stem cell transplantation (HSCT) after myeloablative conditioning rather than autologous… Read more about this study
- Who is it for?
- Ages 16 to 75 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Melphalan, ATG, Fludarabine
- How many people
- 32 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2002to Dec 2010
- Phase
- Phase 2
- 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 16 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- newly-diagnosed AML
- either poor risk cytogenetics and/or bad response to the first cycle of IC defined by more than 10% marrow blasts on day 15
- HLA-compatible donor (maximum one HLA-antigen mismatch)
Who cannot join
- no donor
- Age < 16 years > 75 years
- Cardiac insufficiency requiring treatment or symptomatic coronary artery disease
- Hepatic disease, with AST > 2 times normal
- Severe hypoxemia , pO2 < 70 mm Hg, with decreased DLCO < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted
- Impaired renal function (creatinine > 2 times normal or creatinine clearance < 50% for age, weight, height)
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- HIV-positive patients due to risk of reactivation or acceleration of HIV replication
- Female patients who are pregnant or breast feeding due to risks to fetus from conditioning regimen and potential risks to nursing infants
- Life expectancy severely limited by diseases other than malignancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study of Early Allogeneic Blood Stem Cell Transplantation During Induction-chemotherapy Induced Aplasia in High-risk Acute Myeloid Leukemia
Karyotype is a major prognostic risk factor in patients with acute myeloid leukemia (AML) translating into unfavourable outcome in case of poor-risk cytogenetic aberrations. Several studies have shown that allogeneic hematopoietic stem cell transplantation (HSCT) after myeloablative conditioning rather than autologous HSCT or consolidation chemotherapy result in long-term disease control in this group of patients when achieving a first complete remission. Nevertheless, the complete remission rate achievable is significantly lower than in patients with a more favourable risk profile. In fact, only the minority of AML patients with poor-risk cytogenetics, although having a suitable donor, proceed to HSCT due to refractory disease or infectious complications during induction chemotherapy (IC). Further, new data show that the course of therapy can be estimated as early as two weeks after the initiation of the first course of IC with patients presenting with more than 10 % marrow blasts doing significantly worse than those with a better clearance of blasts. As a result, the chance to obtain a durable remission is considerably low and most patients with bad-risk cytogenetics or failure to achieve blast clearance do not proceed to an allogeneic approach. Together these data indicate that early treatment intensification is warranted in order to provide the potential curative benefit of allogeneic HSCT to the majority of high-risk AML patients.
We have shown that reduced-intensity conditioning (RIC) followed by allogeneic PBSC applied during aplasia after the first cycle of IC in newly-diagnosed high-risk AML patients is feasible and can result in a sustained disease control. These data prompted us to further evaluate in a prospective trial an early "up-front HSCT" in patients with newly-diagnosed high-risk AML defined by karyotype and insufficient blast clearance after the first cycle of IC.
The goal was to provide an allogeneic HSCT as early as possible after diagnosis in AML patients.
Read the detailed description
Only patients with newly-diagnosed AML are eligible for this prospective study. An immediate donor-search, either within the family or in volunteer donor registries, will be performed at diagnosis irrespective of the expected risk profile. All patients will receiv at least one cycle of IC. Inclusion criteria for early allogeneic transplantation are either poor risk cytogenetics and/or bad response to the first cycle of IC defined by more than 10% marrow blasts on day 15. If a patient meets one of those criteria they could enter the early allogeneic HSCT trial after providing informed consent. DNA-based HLA-typing of donor and recipient will be performed using high resolution (4 digits) for HLA - A, B, DRB1 and DQB1 and intermediate resolution (2 digits) for HLA- C.
During IC-induced aplasia after the 1st or 2nd cycle a fludarabine-based reduced intensity conditioning therapy will be started if a donor is available. All patients receive fludarabine 30 mg/m2 i.v. daily for five days (day- 6 to -2) and melphalan 150 mg/m² on day-2. Antithymocyte globulin (ATG Fresenius 10 mg/kg/day day -5 to -2, total dose 40 mg/kg, Fresenius, Bad Homburg, Germany) will be applied after transplantation from unrelated or HLA mismatched family donors. PBSC grafts will be preferred. As immunosuppression cyclosporin A (CsA) is either administered intravenously at a dose of 3 mg/kg/day or given at an bioequivalent amount of the oral formulation in two divided doses starting on the day before blood stem cell infusion (day -1). The dose of CsA is adjusted to maintain blood levels between 150 and 250 ng/ml. Starting on day 50, oral CsA administration will be tapered by 5% weekly if GVHD was inactive. Acute and chronic GvHD will be treated with prednisone, CsA or tacrolimus.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Melphalan, ATG, Fludarabine
- Keywords
- AML, allogeneic transplantation, high-risk, karyotype
- 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.
Melphalan, ATG, FludarabineDrug
allo Tx during aplasia
What is being measured
The primary outcome is the main question the study is designed to answer.
Total and relapse-free survival rate one year after the stem cell transplantation
Measured: 5 years
Secondary outcomes (2)
Incidence of acute GvHD
Measured: 100 days
Safety (evaluated after Common Terminology Criteria for Adverse Events [CTCAE] v 3.0)
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startAug 2002
- Primary completionJul 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Carl Gustav Carus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Martin Bornhauser, Prof, Principal investigator, University hospital Carl Gustav Carus Dresden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00188136
- Sponsor's protocol ID
- DDEATX
- Status last verified
- Dec 2015
- First submitted
- 12 Sep 2005
- Last updated
- 8 Dec 2015
- Results posted
- No
Publications
Platzbecker U, Thiede C, Freiberg-Richter J, Rollig C, Helwig A, Schakel U, Mohr B, Schaich M, Ehninger G, Bornhauser M. Early allogeneic blood stem cell transplantation after modified conditioning therapy during marrow aplasia: stable remission in high-risk acute myeloid leukemia. Bone Marrow Transplant. 2001 Mar;27(5):543-6. doi: 10.1038/sj.bmt.1702819.
PubMed 11313690
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Early Allogeneic Blood Stem Cell Transplantation During Induction-chemotherapy Induced Aplasia in High-risk Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT00188136
- Acronym / sponsor ID
- DDEATX
- Conditions
- Acute Myeloid Leukemia
- Keywords
- AML, allogeneic transplantation, high-risk, karyotype
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University Hospital Carl Gustav CarusUniversity, hospital or other
- Study start
- Aug 2002
- Primary completion
- Jul 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 16 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.
Karyotype is a major prognostic risk factor in patients with acute myeloid leukemia (AML) translating into unfavourable outcome in case of poor-risk cytogenetic aberrations. Several studies have shown that allogeneic hematopoietic stem cell transplantation (HSCT) after myeloablative conditioning rather than autologous HSCT or consolidation chemotherapy result in long-term disease control in this group of patients when achieving a first complete remission. Nevertheless, the complete remission rate achievable is significantly lower than in patients with a more favourable risk profile. In fact, only the minority of AML patients with poor-risk cytogenetics, although having a suitable donor, proceed to HSCT due to refractory disease or infectious complications during induction chemotherapy (IC). Further, new data show that the course of therapy can be estimated as early as two weeks after the initiation of the first course of IC with patients presenting with more than 10 % marrow blasts doing significantly worse than those with a better clearance of blasts. As a result, the chance to obtain a durable remission is considerably low and most patients with bad-risk cytogenetics or failure to achieve blast clearance do not proceed to an allogeneic approach. Together these data indicate that early treatment intensification is warranted in order to provide the potential curative benefit of allogeneic HSCT to the majority of high-risk AML patients.
We have shown that reduced-intensity conditioning (RIC) followed by allogeneic PBSC applied during aplasia after the first cycle of IC in newly-diagnosed high-risk AML patients is feasible and can result in a sustained disease control. These data prompted us to further evaluate in a prospective trial an early "up-front HSCT" in patients with newly-diagnosed high-risk AML defined by karyotype and insufficient blast clearance after the first cycle of IC.
The goal was to provide an allogeneic HSCT as early as possible after diagnosis in AML patients.
Detailed description
Only patients with newly-diagnosed AML are eligible for this prospective study. An immediate donor-search, either within the family or in volunteer donor registries, will be performed at diagnosis irrespective of the expected risk profile. All patients will receiv at least one cycle of IC. Inclusion criteria for early allogeneic transplantation are either poor risk cytogenetics and/or bad response to the first cycle of IC defined by more than 10% marrow blasts on day 15. If a patient meets one of those criteria they could enter the early allogeneic HSCT trial after providing informed consent. DNA-based HLA-typing of donor and recipient will be performed using high resolution (4 digits) for HLA - A, B, DRB1 and DQB1 and intermediate resolution (2 digits) for HLA- C.
During IC-induced aplasia after the 1st or 2nd cycle a fludarabine-based reduced intensity conditioning therapy will be started if a donor is available. All patients receive fludarabine 30 mg/m2 i.v. daily for five days (day- 6 to -2) and melphalan 150 mg/m² on day-2. Antithymocyte globulin (ATG Fresenius 10 mg/kg/day day -5 to -2, total dose 40 mg/kg, Fresenius, Bad Homburg, Germany) will be applied after transplantation from unrelated or HLA mismatched family donors. PBSC grafts will be preferred. As immunosuppression cyclosporin A (CsA) is either administered intravenously at a dose of 3 mg/kg/day or given at an bioequivalent amount of the oral formulation in two divided doses starting on the day before blood stem cell infusion (day -1). The dose of CsA is adjusted to maintain blood levels between 150 and 250 ng/ml. Starting on day 50, oral CsA administration will be tapered by 5% weekly if GVHD was inactive. Acute and chronic GvHD will be treated with prednisone, CsA or tacrolimus.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 16 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- newly-diagnosed AML
- either poor risk cytogenetics and/or bad response to the first cycle of IC defined by more than 10% marrow blasts on day 15
- HLA-compatible donor (maximum one HLA-antigen mismatch)
Key exclusion criteria (9 listed)
- no donor
- Age < 16 years > 75 years
- Cardiac insufficiency requiring treatment or symptomatic coronary artery disease
- Hepatic disease, with AST > 2 times normal
- Severe hypoxemia , pO2 < 70 mm Hg, with decreased DLCO < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted
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 |
|---|---|---|
| Melphalan, ATG, Fludarabineallo Tx during aplasia | Drug | – |
Primary outcome
Total and relapse-free survival rate one year after the stem cell transplantation
Time frame: 5 years
2 secondary outcomes
Incidence of acute GvHD
Time frame: 100 days
Safety (evaluated after Common Terminology Criteria for Adverse Events [CTCAE] v 3.0)
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2015.
- Results publication: PubMed 11313690Platzbecker U, Thiede C, Freiberg-Richter J, Rollig C, Helwig A, Schakel U, Mohr B, Schaich M, Ehninger G, Bornhauser M. Early allogeneic blood stem cell transplantation after modified conditioning therapy during marrow aplasia: stable remission in high-risk acute myeloid leukemia. Bone Marrow Transplant. 2001 Mar;27(5):543-6. doi: 10.1038/sj.bmt.1702819.
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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.
Martin Bornhauser, Prof principal investigator
University hospital Carl Gustav Carus Dresden
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Melphalan, ATG, Fludarabine 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 3 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: finished, as of the sponsor's last update on 8 Dec 2015. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Total and relapse-free survival rate one year after the stem cell transplantation (time frame: 5 years). 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 NCT00188136, which also lists 1 linked publication.
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 8 Dec 2015.