Study to Assess the Safety and Efficacy of Midostaurin (PKC412) in Combination With Standard Chemotherapy During Induction and Consolidation Followed by 12 Months of Monotherapy in Patients With Newly-diagnosed FLT3-mutated Acute Myeloid Leukemia.

An Open-label, Multi-Center, Phase IIIb Study to Assess the Safety and Efficacy of Midostaurin (PKC412) in Patients 18 Years of Age or Older With Newly-diagnosed FLT3-mutated Acute Myeloid Leukemia Who Are Eligible for "7+3" or "5+2" Chemotherapy

ClinicalTrials.gov Identifier: NCT03379727

Novartis Reference Number: CPKC412A2408

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

The purpose of this study is to gather and evaluate additional safety and efficacy data on the combination of midostaurin and standard of care for adult patients with newly diagnosed Fms-like tyrosine kinase receptor (FLT3) mutated Acute Myeloid Leukemia (AML) who are eligible for standard induction and consolidation

Condition 
Acute Myeloid Leukemia
Phase 
Phase 3
Overall status 
Recruiting
Enrollment count 
300 participants
Start date 
Feb 13, 2018
Completion date 
Jan 31, 2022
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Midostaurin
Orally administered inhibitor of multiple tyrosine kinases

Eligibility Criteria

Inclusion Criteria:

Patients eligible for inclusion in this study have to meet all of the following criteria:

Written informed consent must be obtained prior to any screening procedures.
Patients must be 18 years of age or older at the time of signing informed consent.
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).
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.
Patients must have started "7+3" or "5+2" first induction chemotherapy regimen.
Patients must have a documented FLT3 mutation (ITD or TKD).).
Patients must have an ECOG Performance Status of ≤ 2
Patients requiring intrathecal chemotherapy must have a minimum washout of 48 hours prior to the first dose of midostaurin
Patients must have Total Bilirubin ≤ 2.5 x ULN
Patients must have Serum Creatinine ≤ 2.5 x ULN
Patients must be able to communicate well with the investigator to understand and comply with the requirements of the study
Women of child-bearing potential must have a negative pregnancy test before starting use of midostaurin.

Exclusion criteria:

Patients eligible for this study must not meet any of the following criteria:

Prior therapy for AML with the following exceptions:

emergency leukapheresis
emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 7 days
cranial RT for CNS leukostasis (one dose only)
growth factor/cytokine support
Patients with 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
Patients with any pulmonary infiltrate including those suspected to be of infectious origin (unless resolved to ≤ Grade 1 within screening timeframe)
Patients with any uncontrolled illness, including, but not limited to, acute or chronic pancreatitis or uncontrolled infection
QTc >470 msec on screening ECG.
History of hypersensitivity to any drugs or metabolites of similar chemical classes as the study treatment.
Participation in a prior investigational interventional (drug) study with administration of the investigational product within 30 days or 5 half-lives of the investigational product, whichever is longer.

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.

Patients enrolled in this study are not permitted to participate in additional parallel study drug or device studies.

Study Locations

Bulgaria
Novartis Investigative Site
Active, not recruiting
Pleven, 5800
-
Bulgaria
Novartis Investigative Site
Completed
Sofia, 1413
-
Bulgaria
Novartis Investigative Site
Active, not recruiting
Sofia, 1756
-
Bulgaria
Novartis Investigative Site
Completed
Varna, 9000
-
Bulgaria
Croatia
Novartis Investigative Site
Completed
Zagreb, 10000
-
Croatia
Czechia
Novartis Investigative Site
Completed
Brno, 625 00
-
Czechia
Novartis Investigative Site
Completed
Praha 10, 100 34
-
Czechia
Estonia
Novartis Investigative Site
Completed
Tallinn, 13419
-
Estonia
Finland
Novartis Investigative Site
Completed
Helsinki, FIN 00290
-
Finland
Novartis Investigative Site
Completed
Oulu, FIN-90220
-
Finland
Novartis Investigative Site
Active, not recruiting
Tampere, 33521
-
Finland
France
Novartis Investigative Site
Completed
Bayonne, 64109
Bayonne Cedex
France
Novartis Investigative Site
Active, not recruiting
Saint Priest en Jarez, 42270
Loire
France
Novartis Investigative Site
Completed
Besancon cedex, 25030
-
France
Novartis Investigative Site
Active, not recruiting
Clamart, 92141
-
France
Novartis Investigative Site
Active, not recruiting
Creteil, 94010
-
France
Novartis Investigative Site
Active, not recruiting
Dijon, 21034
-
France
Novartis Investigative Site
Completed
Lille Cedex, 59037
-
France
Novartis Investigative Site
Active, not recruiting
Limoges cedex, 87042
-
France
Novartis Investigative Site
Completed
Lyon Cedex, 69373
-
France
Novartis Investigative Site
Active, not recruiting
Metz, 57085
-
France
Novartis Investigative Site
Active, not recruiting
Nice cedex 3, 06202
-
France
Novartis Investigative Site
Completed
Paris, 75010
-
France
Novartis Investigative Site
Completed
Paris, 75012
-
France
Novartis Investigative Site
Active, not recruiting
Pierre Benite Cedex, 69495
-
France
Novartis Investigative Site
Active, not recruiting
Poitiers, 86000
-
France
Novartis Investigative Site
Completed
Villejuif Cedex, 94800
-
France
Greece
Novartis Investigative Site
Withdrawn
Athens, 115 27
GR
Greece
Novartis Investigative Site
Withdrawn
Athens, 106 76
-
Greece
Hungary
Novartis Investigative Site
Completed
Budapest, 1085
-
Hungary
Novartis Investigative Site
Withdrawn
Debrecen, 4032
-
Hungary
Novartis Investigative Site
Withdrawn
Pecs, 7624
-
Hungary
Novartis Investigative Site
Completed
Szeged, H 6725
-
Hungary
Italy
Novartis Investigative Site
Completed
Ancona, 60126
AN
Italy
Novartis Investigative Site
Completed
Avellino, 83100
AV
Italy
Novartis Investigative Site
Active, not recruiting
Bergamo, 24127
BG
Italy
Novartis Investigative Site
Completed
Bologna, 40138
BO
Italy
Novartis Investigative Site
Active, not recruiting
Brescia, 25123
BS
Italy
Novartis Investigative Site
Completed
Cuneo, 12100
CN
Italy
Novartis Investigative Site
Active, not recruiting
Cosenza, 87100
CS
Italy
Novartis Investigative Site
Completed
San Giovanni Rotondo, 71013
FG
Italy
Novartis Investigative Site
Completed
Firenze, 50134
FI
Italy
Novartis Investigative Site
Active, not recruiting
Genova, 16132
GE
Italy
Novartis Investigative Site
Completed
Genova, 16132
GE
Italy
Novartis Investigative Site
Completed
Lecce, 73100
LE
Italy
Novartis Investigative Site
Completed
Latina, 04100
LT
Italy
Novartis Investigative Site
Active, not recruiting
Monza, 20900
MB
Italy
Novartis Investigative Site
Active, not recruiting
Milano, 20122
MI
Italy
Novartis Investigative Site
Completed
Milano, 20132
MI
Italy
Novartis Investigative Site
Completed
Milano, 20162
MI
Italy
Novartis Investigative Site
Completed
Rozzano, 20089
MI
Italy
Novartis Investigative Site
Active, not recruiting
Modena, 41124
MO
Italy
Novartis Investigative Site
Active, not recruiting
Palermo, 90146
PA
Italy
Novartis Investigative Site
Completed
Palermo, 90146
PA
Italy
Novartis Investigative Site
Completed
Piacenza, 29100
PC
Italy
Novartis Investigative Site
Completed
Padova, 35128
PD
Italy
Novartis Investigative Site
Completed
Pescara, 65124
PE
Italy
Novartis Investigative Site
Active, not recruiting
Perugia, 06100
PG
Italy
Novartis Investigative Site
Completed
Parma, 43100
PR
Italy
Novartis Investigative Site
Withdrawn
Pavia, 27100
PV
Italy
Novartis Investigative Site
Completed
Reggio Emilia, 42123
RE
Italy
Novartis Investigative Site
Active, not recruiting
Roma, 00128
RM
Italy
Novartis Investigative Site
Completed
Roma, 00133
RM
Italy
Novartis Investigative Site
Completed
Roma, 00161
RM
Italy
Novartis Investigative Site
Active, not recruiting
Roma, 00168
RM
Italy
Novartis Investigative Site
Withdrawn
Pagani, 84016
SA
Italy
Novartis Investigative Site
Completed
Salerno, 84131
SA
Italy
Novartis Investigative Site
Active, not recruiting
Siena, 53100
SI
Italy
Novartis Investigative Site
Withdrawn
Orbassano, 10043
TO
Italy
Novartis Investigative Site
Completed
Torino, 10128
TO
Italy
Novartis Investigative Site
Active, not recruiting
Venezia, 30174
VE
Italy
Novartis Investigative Site
Completed
Verona, 37126
VR
Italy
Novartis Investigative Site
Completed
Napoli, 80131
-
Italy
Novartis Investigative Site
Completed
Napoli, 80132
-
Italy
Lithuania
Novartis Investigative Site
Active, not recruiting
Vilnius, LT-08661
-
Lithuania
Norway
Novartis Investigative Site
Withdrawn
Lorenskog, 1478
Oslo
Norway
Novartis Investigative Site
Active, not recruiting
Bergen, 5021
-
Norway
Romania
Novartis Investigative Site
Withdrawn
Bucharest, 022328
District 2
Romania
Novartis Investigative Site
Withdrawn
Tg Mures, 540136
Mures
Romania
Novartis Investigative Site
Recruiting
Tg Mures, 540136
Mures
Romania
Novartis Investigative Site
Completed
Craiova, 200136
-
Romania
Novartis Investigative Site
Active, not recruiting
Iasi, 700483
-
Romania
Serbia
Novartis Investigative Site
Active, not recruiting
Belgrade, 11000
-
Serbia
Slovakia
Novartis Investigative Site
Completed
Bratislava, 833 10
Slovak Republic
Slovakia
Novartis Investigative Site
Completed
Banska Bystrica, 975 17
-
Slovakia
Novartis Investigative Site
Completed
Bratislava, 85107
-
Slovakia
Novartis Investigative Site
Withdrawn
Martin, 036 59
-
Slovakia
Spain
Novartis Investigative Site
Active, not recruiting
Barcelona, 08026
Cataluna
Spain
Novartis Investigative Site
Active, not recruiting
Barcelona, 08036
Catalunya
Spain
Novartis Investigative Site
Active, not recruiting
Palma De Mallorca, 07120
Islas Baleares
Spain
Novartis Investigative Site
Completed
Pozuelo de Alarcon, 28223
Madrid
Spain
Novartis Investigative Site
Active, not recruiting
Gasteiz, 01009
País Vasco
Spain
Novartis Investigative Site
Active, not recruiting
La Laguna, 38320
Santa Cruz De Tenerife
Spain
Novartis Investigative Site
Completed
Las Palmas de Gran Canaria, 35010
-
Spain
Novartis Investigative Site
Completed
Leon, 24080
-
Spain
Novartis Investigative Site
Completed
Madrid, 28006
-
Spain
Novartis Investigative Site
Completed
Madrid, 28046
-
Spain
Novartis Investigative Site
Active, not recruiting
Valencia, 46026
-
Spain
Sweden
Novartis Investigative Site
Completed
Boras, 501 82
-
Sweden
Novartis Investigative Site
Completed
Uppsala, SE-751 85
-
Sweden

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Name: 
Novartis Pharmaceuticals
Phone: 
Email: 

Have a question?

Call 1-999-669-6682 or email [email protected]