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

• Status: Terminated
• Trial end date: 2021-02-28
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sebastian Scholl, PD Dr. med.; University of Jena
• Collaborator: Ludwig-Maximilians - University of Munich
• Treatments: Midostaurin; Staurosporine

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• 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