Ignite Creation Date:
2024-05-05 @ 11:56 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00188136
Status:
COMPLETED
Last Update Posted:
2015-12-08
First Post:
2005-09-12
Brief Title:
Early Allogeneic Blood Stem Cell Transplantation in High-risk Acute Myeloid Leukemia AML
Sponsor:
University Hospital Carl Gustav Carus
Organization:
University Hospital Carl Gustav Carus
Study Overview
Official Title:
Phase II Study of Early Allogeneic Blood Stem Cell Transplantation During Induction-chemotherapy Induced Aplasia in High-risk Acute Myeloid Leukemia
Status:
COMPLETED
Status Verified Date:
2015-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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
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 andor 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 mgm2 iv daily for five days day- 6 to -2 and melphalan 150 mgm² on day-2 Antithymocyte globulin ATG Fresenius 10 mgkgday day -5 to -2 total dose 40 mgkg 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 mgkgday 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 ngml 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
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 mgm2 iv daily for five days day- 6 to -2 and melphalan 150 mgm² on day-2 Antithymocyte globulin ATG Fresenius 10 mgkgday day -5 to -2 total dose 40 mgkg 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 mgkgday 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 ngml 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None