A clinical trial of midostaurin in adult patients = 18 years old with newly diagnosed acute myeloid leukemia (AML). Patients must have a mutationknown as FLT3 and eligible for 7+3 or 5+2 chemotherapy
- Conditions
- ewly diagnosed FLT3 mutated acute myeloid leukemiaMedDRA version: 20.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-004440-12-IT
- Lead Sponsor
- OVARTIS PHARMA AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 300
1. Written informed consent must be obtained prior to any screening procedures.
2. Patients must be 18 years of age or older at the time of signing informed consent.
3. Patients must have a documented unequivocal diagnosis of AML according to WHO 2008 classification. A bone marrow or blood blast
count of =20% is required, except for AML with t(15;17), t(8;21), inv(16) or t(16;16)) where blast count may be <20%, and excluding M3
(acute promyelocytic leukemia).
4. Patients with secondary AML are eligible, e.g. patients with antecedent history of treatment for prior malignancy. AML patients with a history of antecedent treatment for myelodysplasia (MDS), e.g. azacitidine or decitabine, remain eligible for treatment on this study. These agents must have been discontinued for a period of at least 30
days or 5 half-lives of the drug (whichever is greater) before midostaurin can be administered.
5. Patients must have started 7+3 or 5+2 first induction chemotherapy regimen.
6. Patients must have a documented FLT3 mutation (ITD or TKD).
7. Patients must have an ECOG Performance Status of = 2
8. Patients requiring intrathecal chemotherapy must have a minimum washout of 48 hours prior to the first dose of midostaurin
9. Patients must have Total Bilirubin = 2.5 x ULN.
10. Patients must have Serum Creatinine = 2.5 x ULN.
11. Patients must be able to communicate well with the investigator to understand and comply with the requirements of the study.
12. Women of child-bearing potential must have a negative pregnancy test before starting use of midostaurin.
Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 210
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90
1. Prior therapy for AML with the following exceptions:
a. emergency leukapheresis
b. emergency treatment for hyperleukocytosis with hydroxyurea for = 7
days
c. cranial RT for CNS leukocytosis (one dose only)
d. growth factor/cytokine support
2. Patients with Left Ventricular Ejection Fraction (LVEF) less than 45%
(by echocardiogram or MUGA) or symptomatic congestive heart failure
(Class III or IV) according to New York Heart Association (NYHA)
classification
3. Patients with any pulmonary infiltrate including those suspected to be
of infectious origin (unless resolved to < Grade 1 within screening
timeframe)
4. Patients with any uncontrolled illness, including, but not limited to,
acute or chronic pancreatitis or uncontrolled infection
5. QTc >470 msec on screening ECG.
6. History of hypersensitivity to any drugs or metabolites of similar
chemical classes as the study treatment.
7. Participation in a prior investigational interventional (drug) study with
administration of the investigational product within 30 days or 5 halflives
of the investigational product, whichever is longer.
8. 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.
9. Patients enrolled in this study are not permitted to participate in
additional parallel study drug or device studies.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To further assess the safety of midostaurin in induction, consolidation<br>and maintenance therapy, including, the 7+3 regimen, daunorubicin<br>(60-90mg/m2/day), the substitution of daunorubicin by idarubicin and<br>cytarabine (100-200 mg/m2/day) and also allowing the 5+2 reduced<br>dose regimen.;Secondary Objective: To assess the clinical efficacy of midostaurin in combination with<br>chemotherapy regimens in induction and consolidation and the clinical<br>efficacy of midostaurin maintenance phase (measured by CR/CRi rate).;Primary end point(s): Proportion of patients with AEs, Grade 3&4 AEs, SAEs, AEs leading to discontinuation, and deaths.;Timepoint(s) of evaluation of this end point: At end of study
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Proportion of patients with CR/CRi as per local assessment;Timepoint(s) of evaluation of this end point: At end of study