Clinical trial NCT02624570: Midostaurin Access Program for Newly Diagnosed FLT3 (ITD or TKD) Mutated AML Adult Patients Eligible for Standard Induction and Consolidation Chemotherapy
Official title: An Open-label, Multi-center, Expanded Treatment Protocol of Midostaurin (PKC412) in Adult Patients With Newly Diagnosed Fms-like Tyrosine Kinase Receptor (FLT3) Mutated Acute Myeloid Leukemia (AML) Who Are Eligible for Standard Induction and Consolidation Chemotherapy.
Study type: EXPANDED_ACCESS
Overall status: NO_LONGER_AVAILABLE
Conditions: Acute Myeloid Leukemia (AML) With
FLT3 Mutation, Internal Tandem Duplication (ITD) or Tyrosine Kinase Domain (TKD)
Keywords: AML
FLT3
ITD
TKD
acute myeloid leukemia
induction
consolidation
continuation
EAP
ETP
midostaurin
PKC412
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-12-08
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no

Brief summary: The purpose of this study is to provide access to Midostaurin and gather additional safety 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 chemotherapy.

Detailed description: The purpose of this study is to provide Midostaurin (study drug) treatment to newly diagnosed FLT3 mutated (ITD or TKD) AML adult patients (18 years or older) eligible for standard standard induction (cytarabine + daunorubicin/Idarubicin) and consolidation (cytarabine) chemotherapy.

Eligibility criteria: Inclusion Criteria:

Written informed consent must be obtained prior to any screening procedures. Patients must meet all Inclusion Criteria:

* Patient is able to communicate well with the investigator, to understand and comply with the requirements of the study.
* Patients must be 18 years of age or older; elderly patients must be fit to receive intensive induction and consolidation chemotherapy
* Patients must have a documented FLT3 mutation (ITD or TKD)
* Patients must have an ECOG Performance Status of ≤ 2
* Patients must have a documented unequivocal diagnosis of AML according to WHO 2008 classification (\>20% blasts in the bone marrow and/or peripheral blood), excluding M3 (acute promyelocytic leukemia).
* Patients requiring intrathecal chemotherapy must have a minimum washout of 48 hours prior to the first dose of midostaurin
* 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.
* Secondary AML, e.g. patients with antecedent history of treatment for prior malignancy Patients must have the following laboratory values (Direct Bilirubin ≤ 2.5 x ULN, Serum Creatinine ≤ 2.5 x ULN)

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 ≤ 5 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 uncontrolled illness, including, but not limited to, acute or chronic pancreatitis or uncontrolled infection
* QTc \>500 msec on screening ECG. History of hypersensitivity to any drugs or metabolites of similar chemical classes as the IMP.
* 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.
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods.
* Sexually active males should not father a child during this study and for upto 5 months following.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Berkeley
country: United States
facility: The Jordan Research and Education Center ABSMC Comprehensive Cancer Ctr
state: California
city: Duarte
country: United States
facility: City of Hope National Medical Center Department of Hematology & HCT
state: California
city: Fullerton
country: United States
facility: St. Judes Medical Center
state: California
city: Orange
country: United States
facility: University of Calif Irvine Medical Center Family Comp Cancer Cntr
state: California
city: Denver
country: United States
facility: Kaiser Permanente Northwest Kaiser
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Hospital Poudre Valley Hospital -U of C
state: Colorado
city: Hollywood
country: United States
facility: Memorial Healthcare System Memorial Healthcare System
state: Florida
city: Orlando
country: United States
facility: UF Health Cancer Center at Orlando Health Orlando Health
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute SC - 5
state: Florida
city: Augusta
country: United States
facility: Augusta University Georgia Cancer Center Pharmacy
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center Dept.of Rush UniversityMedCtr.
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Beech Grove
country: United States
facility: Indiana Blood and Marrow Institute Indiana Blood and Marrow Trans
state: Indiana
city: Fort Wayne
country: United States
facility: Ft Wayne Medical Oncology and Hematology Inc
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute Norton Cancer Institute
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville / James Graham Brown Cancer Center Louisville 529-539
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute Harper Hosp. Invest. Pharmacy
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital SC
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: Nebraska Cancer Specialist/Missouri Valley Cancer Consortium
state: Nebraska
city: Las Vegas
country: United States
facility: Healthcare Partners Medical Group
state: Nevada
city: New York
country: United States
facility: Weill Cornell Medical College NY Presbyterian Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center Univ of Rochester (7)
state: New York
city: Clackamas
country: United States
facility: Kaiser Permanente NW Region Kaiser Permanente Northwest
state: Oregon
city: Hershey
country: United States
facility: Penn State University / Milton S. Hershey Medical Center Penn State Cancer Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center University of Pen/Abr Canc ctr
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina Hematology-Oncology Division
state: South Carolina
city: Chattanooga
country: United States
facility: Erlanger Medical Center Erlanger Health System
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center, Clinical Trials Center Division Hematology/Oncology
state: Tennessee
city: Galveston
country: United States
facility: University of Texas Medical Branch University of Texas MB
state: Texas
city: Houston
country: United States
facility: McGovern Medical School at the University of Texas Health
state: Texas
city: Houston
country: United States
facility: Oncology Consultants Oncology Consultants
state: Texas
city: San Antonio
country: United States
facility: Methodist Healthcare System
state: Texas
city: Murray
country: United States
facility: Intermountain Healthcare - Huntsman Cancer Clinics Intermountain Healthcare (2)
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute Univ of Utah
state: Utah
city: Norfolk
country: United States
facility: Virginia Oncology Associates Virginia Oncology Assoc. (6)
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Veterans Affairs Puget Sound Health Care System VAMC Seattle, WA Divison
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Hospital and Clinics
state: Washington
city: Cheyenne
country: United States
facility: Cheyenne Regional Medical Center
state: Wyoming
Study officials:
References:
citation: Roboz GJ, Strickland SA, Litzow MR, Dalovisio A, Perl AE, Bonifacio G, Haines K, Barbera A, Purkayastha D, Sweet K. Updated safety of midostaurin plus chemotherapy in newly diagnosed FLT3 mutation-positive acute myeloid leukemia: the RADIUS-X expanded access program. Leuk Lymphoma. 2020 Dec;61(13):3146-3153. doi: 10.1080/10428194.2020.1805109. Epub 2020 Aug 19.