Midostaurin in acute myeloid leukemia after allogeneic stem cell transplantatio
- Conditions
- Acute Myeloid LeukemiaMedDRA version: 21.1Level: LLTClassification code 10066764Term: Acute myeloid leukaemia progressionSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2019-000136-26-DE
- Lead Sponsor
- Friedrich-Schiller-Universität Jena
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 86
• Patients with molecular relapse or persistent molecular positivity of AML after allogeneic SCT
• Detection of FLT3-ITD or FLT3-TKD at primary diagnosis or at antecedent relapse of AML prior to allogeneic SCT
• Sensitive MRD assessment based on qPCR (i.e. low PCR cut off” for each applied MRD marker of at least 0.1% - e.g. NPM1mut/ABL1)
• ANC > 1,0 Gpt/L and Platelets > 50 Gpt/L
• ECOG performance status 0-2
• GFR > 30 ml/min and serum bilirubin < 1.5 x ULN
• Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) = 3.0 × ULN;
Serum levels of potassium (3.3-4.5 mmol/L), magnesium (0.77-1.03 mmol/L), total calcium (2.2- 2.65 mmol/L) or within the normal limits (=LLN [lower limit of normal] and =ULN [upper limit of normal]) of the hospital or local laboratory. Correction of electrolytes levels with supplements to fulfil inclusion criteria is allowed.
• All female patients with reproductive potential and all male patients must agree to use effective methods to prevent pregnancy. Female patients of childbearing potential must agree to use dual methods of contraception (i.e. with progesterone contraceptive implants, intrauterine device with progesterone, pills containing estrogen and progestin, as well as three-month injection with depot progestin) for the duration of the study. Male patients and male partners of female patients must agree to use a barrier method of contraception for the duration of the study if sexually active with a female of childbearing potential. It is required that sexually active men use condom during intercourse while taking the drug and for 2 weeks after stopping treatment and not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Female partners of male patients must be advised to use a highly effective method of contraception. Contraception and a hold on sperm donation for male patients are to be continued for at least 2 weeks after the last dose of midostaurin for safety reasons.
• All women of child-bearing potential have to complete a serum pregnancy test at screening visit. After screening, monthly serum pregnancy tests must be performed by all enrolled women of child-bearing potential from start of midostaurin until stop of midostaurin. If a test result indicates a pregnancy, the patient must stop treatment with midostaurin immediately. Pregnancy testing is not required for women who are determined to be post-menopausal.
• Written informed consent prior to any study procedures being performed
• Age = 18 years
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 29
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 57
• Acute promyelocytic leukemia (APL)
• Hematological relapse of AML (bone marrow blasts =5% or reappearance of blasts in the blood or development of extramedullary disease)
• Lack of a suitable MRD marker (no detectable MRD marker at diagnosis or low sensitivity of an available MRD marker, e.g. sensitivity > 0.1% MRD transcript/ABL1)
• Impaired left ventricular 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
• 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 enrolment or who have not recovered from side effects of such therapy
• Patients with resting QTcF =450 msec prior to enrolment or inability to determine the QTcF interval. Other clinically significant heart disease (e.g. unstable angina, congestive heart failure) Other concurrent uncontrolled medical conditions (e.g., active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol
• Substance abuse, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method