- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03686345
Midostaurin Associated With Standard Chemotherapy in Patients With Core-binding Factor Leukemia (AML FLT3)
Prospective Evaluation of a Continuation Therapy With Midostaurin in Adult Patients With Core-binding Factor Leukemia and Integrated Genetic Analysis: a Multi-center Phase II Study
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Roberto Cairoli, MD
- Phone Number: 2668 0039026444
- Email: roberto.cairoli@ospedaleniguarda.it
Study Contact Backup
- Name: Eirika Ravelli, MD
- Phone Number: 2668 0039026444
- Email: erika.ravelli@ospedaleniguarda.it
Study Locations
-
-
-
Milano, Italy, 20162
- Recruiting
- Ospedale Cà Granda - Niguarda S.C: Ematologia
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Contact:
- Roberto Cairoli, MD
- Phone Number: 2668 +39 02 64444
- Email: roberto.cairoli@ospedaleniguarda.it
-
Contact:
- Erika Ravelli, MD
- Phone Number: 2668 0039026444
- Email: erika.ravelli@ospedaleniguarda.it
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Principal Investigator:
- Roberto Cairoli, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Written informed consent must be obtained prior to any screening procedures.
- Patients must be 18 to 65 years of age at the time of signing informed consent.
- Patients must have an unequivocal diagnosis of de novo-CBFL, prior to start midostaurin, documented by rearrangement of Core Binding Factor (CBF) genes, namely AML1-ETO and CBFB-MYH11, either with observation of t(8;21)(q22;q22) or inv(16)(p13; q32)/t(16;16)(p13; q32) by conventional cytogenetics or hybridization techniques or detection of fusion genes by PCR-polymerase chain reaction
- Patients must be fit to receive an anthracycline/AraC-based induction therapy (i.e. Ara-C 100 mg/m2 or 200 mg/m2 i.v. day, by continuous infusion for 7 days and Idarubicin 12 mg/m2 i.v. day or daunomycin 60 mg/m2 on days 1, 3 and 5)
- Patients must have an ECOG-Eastern Cooperative Oncology Group Performance Status of ≤ 2.
- Patients must have Total Bilirubin ≤ 1.5 x ULN, and AST or ALT ≤ 2.5 x ULN.
- Patients must have Serum Creatinine ≤ 1.5 x ULN.
- Women of child-bearing potential must have a negative pregnancy test before starting the protocol.
Exclusion Criteria:
Prior therapy for AML with the following exceptions:
- emergency leukapheresis
- emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 7 days
- Central nervous system involvement
- Presence of any uncontrolled bacterial, viral or fungal infection
- Known human immunodeficiency virus (HIV) positive
- An active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection. Patients whose disease is controlled under antiviral therapy should not be excluded.
- Presence of other active malignancies
- QTc > 470 msec (Bazett formula) on screening ECG
Presence of significant uncontrolled or active cardiovascular disease, specifically including, but not restricted to:
- Myocardial infarction, unstable angina and/or congestive heart failure within 3 months prior to randomization
- History of clinically significant (as determined by the treating physician) atrial arrhythmia or any ventricular arrhythmia
- Uncontrolled hypertension
- Taking medications that are known to be associated with Torsades de Pointes.
- History of hypersensitivity to any drugs or metabolites of similar chemical classes as the study treatment.
- Pregnancy statements and contraception requirements:
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for at least 4 months after stopping medication. Highly effective contraception methods include:
- Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
- Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
- Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject
- Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system, or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should also add a barrier method of contraception, particularly as it is currently unknown whether midostaurin may reduce the effectiveness of hormonal contraceptives. Sexually-active males unless they use a condom during intercourse with females of reproductive potential or pregnant women and for at least 4 months after stopping treatment to avoid conception or embryo-fetal harm.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Core binding factor acute myeloid leukemia (CBF-AML)
Patients must have an unequivocal diagnosis of de novo-CBFL, prior to start midostaurin, documented by rearrangement of Core Binding Factor (CBF) genes, namely AML1-ETO and CBFB-MYH11.
The experimental arm involves the administration of Midostaurin orally 50 mg (two 25 mg tablets) twice a day, from the end of induction chemotherapy, for 14 days.
Patients should take Midostaurin at approximately 12 hours intervals.
During all consolidation cycles, Midostaurin 50 mg (two 25 mg tablets) is administered orally twice a day, on days 8-21.
Patients in complete remission after 3 cycles of remission consolidation therapy, will receive Midostaurin continuation therapy for 12 months.
Midostaurin 50 mg (two 25 mg tablets) will be given orally twice a day for 12 months.
|
Midostaurin associated with standard chemotherapy in patients with core-binding factor leukemia
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Relapse Incidence
Time Frame: 2 years
|
To show that the percentage of relapsed patients is 28% or below
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: 5 years
|
To determine overall survival from achievement of first complete remission
|
5 years
|
Safety assessment - Frequency and severity of adverse events
Time Frame: Up to 30 days after last dose of study drug
|
Incidence of toxicity, defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.
Frequency and severity of adverse events will be collected and summarized by descriptive statistics.
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
An adverse event is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained.
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Up to 30 days after last dose of study drug
|
Disease-free survival
Time Frame: 5 years
|
To determine disease-free survival from achievement of first complete remission
|
5 years
|
Event-free survival
Time Frame: 5 years
|
To determine event-free survival from diagnosis
|
5 years
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- REL-AML 001/2017
- 2017-002094-18 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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