Acute Myeloid Leukemia, AdultPhase 2NCT03951961
Midostaurin in MRD (Minimal Residual Disease) Positive Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation
A Phase 2 study testing Midostaurin in people with Acute Myeloid Leukemia, Adult, run by University of Jena at 4 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Adult
- What is being tested?
- Midostaurin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 4 sitesGermany
- Study dates
- 20 Mar 2020to 28 Feb 2021
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with molecular relapse or persistent molecular positivity of AML after allogeneic SCT (stem cell Transplantation)
- Detection of FLT3-ITD (Internal tandem duplication) or FLT3-TKD (tyrosine kinase domain) at primary diagnosis or at antecedent relapse of AML prior to allogeneic SCT
- Sensitive MRD assessment based on qPCR (e.g. by means of NPM1 mutations)
- absolute neutrophil count > 1,0 Gpt/L and Platelets > 50 Gpt/L
- ECOG (Eastern Cooperative Oncology Group) performance status 0-2
- glomerular filtration rate > 30 ml/min and serum bilirubin < 1.5 x upper limit of normal
Show all 10Show fewer
- Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤ 3.0 × ULN
- Normal serum levels of potassium, magnesium, and corrected calcium
- Written informed consent prior to any study procedures being performed
- Age ≥ 18 years
Who cannot join
- Acute promyelocytic leukemia (APL)
- Hematological relapse of AML
- Lack of a suitable MRD marker
- Impaired ejection fraction (LVEF) < 45%
- Patients with midostaurin treatment after allogeneic SCT or with ongoing TKI therapy < 4 weeks prior to inclusion
- Treatment with an investigational drug within 5 half-lives preceding the first dose of study medication
Show all 18Show fewer
- History of acute or chronic pancreatitis
- Active and uncontrolled infections
- History of severe lung disease and/or relevant functional impairment
- Medical indication for treatment with strong CYP3A4 inhibitors (e.g. voriconazole, posaconazole, clarithromycin)
- Positive PCR for Human Immunodeficiency Virus (HIV) or Hepatitis B or C
- Patients unable to swallow medication
- Known hypersensitivity reaction to midostaurin or any excipient of midostaurin
- Concomitant medications with known induction of CYP3A4 isoenzyme unless they can be discontinued or replaced prior to enrollment
- Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
- Patients who are pregnant or breast feeding, or females of reproductive potential not employing an effective method of birth control. Female patients must agree to an effective birth control throughout the study and for up to 4 months beyond.
- Other medical conditions (e.g. corrected QT interval prolongation) that might interfere with midostaurin treatment
- Substance abuse, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
Trial locations and contacts
4 sites in 1 country.
Germany4 sites
Klinikum Chemnitz gGmbH
Chemnitz, 09113
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
Dresden, 01307
Universitätsklinikum Jena
Jena, 07747
Universitätsklinikum Leipzig AöR
Leipzig, 04103
About this study
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.
Read the 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 (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.
- Conditions
- Acute Myeloid Leukemia, Adult
- Being tested
- Midostaurin
- 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.
MidostaurinDrug
50mg Midostaurin bid for 12 months
| Study group | Role | What they receive |
|---|---|---|
| Midostaurin | Experimental | 50 mg Midostaurin bid for 12 months Receives: Drug: Midostaurin |
What is being measured
The primary outcome is the main question the study is designed to answer.
proportion of patients without AML relapse
impact of midostaurin single treatment on Leukemia-free survival (LFS)
Measured: at 12 months after start of midostaurin treatment
Secondary outcomes (5)
number of patients with low MRD (Minimal Residual Disease)
molecular response to midostaurin treatment
Measured: at 3 months after start of midostaurin treatment
Incidence of acute and chronic graft-versus-host disease (GvHD)
Incidence of acute and chronic GvHD
Measured: baseline and every 3 months until 12 months after start of midostaurin treatment
Incidence of adverse events grade 3-5 of midostaurin after allogeneic SCT
Incidence of adverse events grade 3-5
Measured: baseline and every 3 months until 12 months after start of midostaurin treatment
Next-generation sequencing analyses of FLT3-mutation
mechanisms of primary or secondary resistance to midostaurin
Measured: baseline and every 3 months until 12 months after start of midostaurin treatment
quality of life assessment with certified "EORTC QLQ - C30 questionnaire"
quality of life assessment with certified "EORTC QLQ - C30 questionnaire"
Measured: baseline and every 3 months until 12 months after start of midostaurin treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2019
- Study start20 Mar 2020
- Primary completion28 Feb 2021
- Study completion28 Feb 2021
Why it stopped: Insufficient Recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia, AdultStudies 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
- Not applicable
- Intervention model
- Single group
- Model description
- single-arm, multicenter phase II, non-randomized
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Jena
- Sponsor type
- University, hospital or other
- Collaborators
- Ludwig-Maximilians - University of Munich
- Responsible party
- Principal investigator, Sebastian Scholl, PD Dr. med., University of Jena
- Investigators
- Sebastian Scholl, Prof. Dr., Principal investigator, Jena University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03951961
- Sponsor's protocol ID
- MAURITIUS
- Other IDs
- 2019-000136-26, 2019
- Status last verified
- Jan 2022
- First submitted
- 9 May 2019
- Last updated
- 21 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Midostaurin in MRD (Minimal Residual Disease) Positive Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT03951961
- Acronym / sponsor ID
- MAURITIUS
- Conditions
- Acute Myeloid Leukemia, Adult
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient Recruitment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of JenaUniversity, hospital or other
- Collaborators
- Ludwig-Maximilians - University of Munich
- Study start
- 20 Mar 2020 (actual)
- Primary completion
- 28 Feb 2021 (actual)
- Study completion
- 28 Feb 2021 (actual)
- First posted
- 16 May 2019 (actual)
- 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 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 (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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- single-arm, multicenter phase II, non-randomized
| Arm | Type | Receives |
|---|---|---|
| Midostaurin | Experimental | Drug: Midostaurin50 mg Midostaurin bid for 12 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients with molecular relapse or persistent molecular positivity of AML after allogeneic SCT (stem cell Transplantation)
- Detection of FLT3-ITD (Internal tandem duplication) or FLT3-TKD (tyrosine kinase domain) at primary diagnosis or at antecedent relapse of AML prior to allogeneic SCT
- Sensitive MRD assessment based on qPCR (e.g. by means of NPM1 mutations)
- absolute neutrophil count > 1,0 Gpt/L and Platelets > 50 Gpt/L
- ECOG (Eastern Cooperative Oncology Group) performance status 0-2
Key exclusion criteria (18 listed)
- Acute promyelocytic leukemia (APL)
- Hematological relapse of AML
- Lack of a suitable MRD marker
- Impaired ejection fraction (LVEF) < 45%
- Patients with midostaurin treatment after allogeneic SCT or with ongoing TKI therapy < 4 weeks prior to inclusion
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 |
|---|---|---|
| Midostaurin50mg Midostaurin bid for 12 months | Drug | Midostaurin |
Primary outcome
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)
5 secondary outcomes
number of patients with low MRD (Minimal Residual Disease)
Time frame: at 3 months after start of 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 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
Next-generation sequencing analyses of FLT3-mutation
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"
Time frame: baseline and every 3 months until 12 months after start of midostaurin treatment
Results and safety
The study was stopped early (reason given: Insufficient Recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2022.
- Individual participant dataSharing planned: No
Related trials for Acute Myeloid Leukemia, Adult
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 2
Comparing Different Treatment Lengths for Venetoclax in Older People With Newly Diagnosed Acute Myeloid Leukemia (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia
RecruitingPhase 3
Bleximenib in Combination With Standard Induction and Consolidation Therapy Followed by Maintenance for Treatment of Patients With Acute Myeloid Leukemia (AML)
Acute Myeloid Leukemia
RecruitingPhase 2
Testing the Addition of Venetoclax or Gemtuzumab Ozogamicin (GO) to Usual Treatment Regimen (Cytarabine and Daunorubicin, "7+3") for Core Binding Factor Acute Myeloid Leukemia (CBF-AML) to Improve Response (A MYELOMATCH Treatment Trial)
Core Binding Factor Acute Myeloid Leukemia
Enrolling by invitationPhase 1
A Rollover Study for Continued Study Treatment and Ongoing Safety Monitoring
Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Chronic, B-Cell
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.
Sebastian Scholl, Prof. Dr. principal investigator
Jena University Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Midostaurin in people with Acute Myeloid Leukemia, Adult, run by University of Jena at 4 sites 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 10 inclusion and 18 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 21 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 was stopped early (reason given: Insufficient Recruitment). 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?
proportion of patients without AML relapse (time frame: at 12 months after start of midostaurin treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Jan 2022.