Midostaurin in MRD (Minimal Residual Disease) Positive Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation
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|ClinicalTrials.gov Identifier: NCT03951961|
Recruitment Status : Not yet recruiting
First Posted : May 16, 2019
Last Update Posted : May 16, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia, Adult||Drug: Midostaurin||Phase 2|
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 (e.g. 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-1)mutation (i.e. 100 to 1000 copies of mutated NPM1 per 10,000 ABL (Abelson Murine Leukemia Viral Oncogene Homolog) transcripts or 1% to 10% NPM1/ABL, 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||86 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||single-arm, multicenter phase II, non-randomized|
|Masking:||None (Open Label)|
|Official Title:||Midostaurin in MRD (Minimal Residual Disease) Positive Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation|
|Estimated Study Start Date :||July 1, 2019|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||December 31, 2023|
50 mg Midostaurin bid for 12 months
50mg Midostaurin bid for 12 months
- proportion of patients without AML relapse [ Time Frame: at 12 months after start of midostaurin treatment ]impact of midostaurin single treatment on Leukemia-free survival (LFS)
- number of patients with low MRD (Minimal Residual Disease) [ Time Frame: at 3 months after start of midostaurin treatment ]molecular response to midostaurin treatment
- Incidence of acute and chronic graft-versus-host disease (GvHD) [ Time Frame: baseline and every 3 months until 12 months after start of midostaurin treatment ]Incidence of acute and chronic GvHD
- Incidence of adverse events grade 3-5 of midostaurin after allogeneic SCT [ Time Frame: baseline and every 3 months until 12 months after start of midostaurin treatment ]Incidence of adverse events grade 3-5
- Next-generation sequencing analyses of FLT3-mutation [ Time Frame: baseline and every 3 months until 12 months after start of midostaurin treatment ]mechanisms of primary or secondary resistance to midostaurin
- quality of life assessment with certified "EORTC QLQ - C30 questionnaire" [ Time Frame: baseline and every 3 months until 12 months after start of midostaurin treatment ]quality of life assessment with certified "EORTC QLQ - C30 questionnaire"
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03951961
|Contact: Sebastian Scholl, PD Dr. med.||+493641 ext email@example.com|
|Contact: Christian Fabisch, Dr.||+493641 ext firstname.lastname@example.org|
|Universitätsklinikum Jena||Not yet recruiting|
|Jena, Germany, 07747|
|Contact: Sebastian Scholl, PD Dr. med. +49 3641 9324573 email@example.com|
|Principal Investigator:||Sebastian Scholl, PD Dr. med.||Universitätsklinikum Jena|