Midostaurin in MRD (Minimal Residual Disease) Positive Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation

NCT03951961 | Terminated Phase 2

• 2 other identifiers: MAURITIUS2019-000136-26
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 4

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.

Conditions

Acute Myeloid Leukemia, Adult

Outcome Measures

Primary Outcomes (1)

• proportion of patients without AML relapse

  impact of midostaurin single treatment on Leukemia-free survival (LFS)

  at 12 months after start of midostaurin treatment

Secondary Outcomes (5)

• number of patients with low MRD (Minimal Residual Disease)

  at 3 months after start of midostaurin treatment

• Incidence of acute and chronic graft-versus-host disease (GvHD)

  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

  baseline and every 3 months until 12 months after start of midostaurin treatment

• Next-generation sequencing analyses of FLT3-mutation

  baseline and every 3 months until 12 months after start of midostaurin treatment

• quality of life assessment with certified "EORTC QLQ - C30 questionnaire"

  baseline and every 3 months until 12 months after start of midostaurin treatment

Study Arms (1)

Midostaurin

EXPERIMENTAL

50 mg Midostaurin bid for 12 months

Drug: Midostaurin

Interventions

Midostaurin DRUG

50mg Midostaurin bid for 12 months

Midostaurin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• Acute promyelocytic leukemia (APL)
• Hematological relapse of AML
• Lack of a suitable MRD marker
• Impaired ejection fraction (LVEF) \< 45%
• Treatment with an investigational drug within 5 half-lives preceding the first dose of study medication
• 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.

Sponsors & Collaborators

• University of Jena: lead
• Ludwig-Maximilians - University of Munich: collaborator

Study Sites (4)

Klinikum Chemnitz gGmbH

Chemnitz, 09113, Germany

Location

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Jena

Jena, 07747, Germany

Location

Universitätsklinikum Leipzig AöR

Leipzig, 04103, Germany

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

midostaurin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Sebastian Scholl, Prof. Dr.

  Jena University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: single-arm, multicenter phase II, non-randomized

Study Record Dates

• First Submitted: May 9, 2019
• First Posted: May 16, 2019
• Study Start: March 20, 2020
• Primary Completion: February 28, 2021
• Study Completion: February 28, 2021
• Last Updated: January 21, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4)