Ignite Creation Date:
2024-05-06 @ 1:11 PM
Last Modification Date:
2024-10-26 @ 1:10 PM
Study NCT ID:
NCT03951961
Status:
TERMINATED
Last Update Posted:
2022-01-21
First Post:
2019-05-09
Brief Title:
Midostaurin in MRD Minimal Residual Disease Positive Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation
Sponsor:
University of Jena
Organization:
University of Jena
Study Overview
Official Title:
Midostaurin in MRD Minimal Residual Disease Positive Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation
Status:
TERMINATED
Status Verified Date:
2022-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Insufficient Recruitment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The MAURITIUS trial is a single-arm multicenter phase II study of single treatment with midostaurin being applied to AML acute myeloid leukemia patients with activating FLT3 FMS-like tyrosine kinase3 mutations and either molecular relapse or persistent molecular positivity after allogeneic SCT The leukemia-free survival LFS the achievement of MRD low as well as the incidence of GvHD after transplantation reflect the most relevant endpoints of this non-randomized clinical trial
Detailed Description:
The clinical situation of AML acute myeloid leukemia relapse after intensive chemotherapy or even after allogeneic SCT represents a huge challenge in hematology So far no FLT3-TKI Tyrosine kinase Inhibitor has been approved for the treatment of relapsed or refractory AML with activating FLT3 mutations in the European Union
For elderly and unfit patients at primary diagnosis and for patients with AML relapse after induction and consolidation chemotherapy including those with allogeneic SCT who are not eligible for any further intensive treatment approach AML therapy with HMA hypomethylating agents represents the standard of care and is associated with an even worse prognosis in those patients who relapse with AML after transplantation
The FLT3-TKI midostaurin has been approved for newly diagnosed AML patients with activating FLT3 mutations who receive intensive induction and subsequent consolidation chemotherapy including midostaurin maintenance restricted to patients who do not undergo allogeneic SCT So far there is no approval of FLT3-TKI treatment for patients with FLT3-mutated AML after allogeneic SCT Recently preliminary data of the RADIUS trial investigating midostaurin maintenance after allogeneic SCT could demonstrate the feasibility of midostaurin treatment in the setting of post-transplant AML patients Importantly only half of patients were able to complete 12 cycles of maintenance and in most cases midostaurin was prematurely ceased due to a higher rate of adverse events than expected As a consequence of this clinical trial there is a good rationale to investigate midostaurin maintenance after allogeneic SCT focusing on those AML patients with a high risk of hematologic relapse after transplantation
In detail MRD assessment provides a reliable method in the majority of patients with FLT3-mutated AML eg by qPCR to identify AML patients with the highest risk of relapse following allogeneic SCT There are consistent data demonstrating that MRD positivity by means of NPM1 Nuclophosphmin-1mutation ie 100 to 1000 copies of mutated NPM1 per 10000 ABL Abelson Murine Leukemia Viral Oncogene Homolog transcripts or 1 to 10 NPM1ABL respectively is associated with a 60-90 risk of hematologic relapse
Thus this clinically relevant subgroup of AML patients with activating FLT3 mutations who develop a molecular relapse or who are characterized by a persistent MRD positivity after intensive AML treatment represents the target population of this clinical trial The rationale of this study is to treat AML patients with MRD positivity using single midostaurin treatment and to improve the clinical outcome of these patients by preventing hematologic relapse after allogeneic SCT by targeted therapy against activating FLT3 mutations
For elderly and unfit patients at primary diagnosis and for patients with AML relapse after induction and consolidation chemotherapy including those with allogeneic SCT who are not eligible for any further intensive treatment approach AML therapy with HMA hypomethylating agents represents the standard of care and is associated with an even worse prognosis in those patients who relapse with AML after transplantation
The FLT3-TKI midostaurin has been approved for newly diagnosed AML patients with activating FLT3 mutations who receive intensive induction and subsequent consolidation chemotherapy including midostaurin maintenance restricted to patients who do not undergo allogeneic SCT So far there is no approval of FLT3-TKI treatment for patients with FLT3-mutated AML after allogeneic SCT Recently preliminary data of the RADIUS trial investigating midostaurin maintenance after allogeneic SCT could demonstrate the feasibility of midostaurin treatment in the setting of post-transplant AML patients Importantly only half of patients were able to complete 12 cycles of maintenance and in most cases midostaurin was prematurely ceased due to a higher rate of adverse events than expected As a consequence of this clinical trial there is a good rationale to investigate midostaurin maintenance after allogeneic SCT focusing on those AML patients with a high risk of hematologic relapse after transplantation
In detail MRD assessment provides a reliable method in the majority of patients with FLT3-mutated AML eg by qPCR to identify AML patients with the highest risk of relapse following allogeneic SCT There are consistent data demonstrating that MRD positivity by means of NPM1 Nuclophosphmin-1mutation ie 100 to 1000 copies of mutated NPM1 per 10000 ABL Abelson Murine Leukemia Viral Oncogene Homolog transcripts or 1 to 10 NPM1ABL respectively is associated with a 60-90 risk of hematologic relapse
Thus this clinically relevant subgroup of AML patients with activating FLT3 mutations who develop a molecular relapse or who are characterized by a persistent MRD positivity after intensive AML treatment represents the target population of this clinical trial The rationale of this study is to treat AML patients with MRD positivity using single midostaurin treatment and to improve the clinical outcome of these patients by preventing hematologic relapse after allogeneic SCT by targeted therapy against activating FLT3 mutations
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2019-000136-26 | EUDRACT_NUMBER | None | None |