Clinical trial NCT01721876: Volasertib in Combination With Low-dose Cytarabine in Patients Aged 65 Years and Above With Previously Untreated Acute Myeloid Leukaemia, Who Are Ineligible for Intensive Remission Induction Therapy (POLO-AML-2)
Official title: A Phase III Randomised, Double-blind, Controlled, Parallel Group Study of Intravenous Volasertib in Combination With Subcutaneous Low-dose Cytarabine vs. Placebo + Low-dose Cytarabine in Patients >=65 Years With Previously Untreated Acute Myeloid Leukaemia, Who Are Ineligible for Intensive Remission Induction Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Leukemia, Myeloid, Acute
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2012-11-06
Enrollment: 666
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate the efficacy, safety, and pharmacokinetics of intravenous volasertib + subcutaneous low dose cytarabine in patients \>= 65 years of age with previously untreated acute myeloid leukaemia, ineligible for intensive remission induction therapy


Eligibility criteria: Inclusion criteria:

1. Age \>= 65years.
2. Cytologically/histologically confirmed acute myeloid leukaemia (AML) according to WHO classification; (except for acute promyelocytic leukaemia (APL).
3. Previously untreated AML (except for hydroxyurea and/or corticosteroid therapy for no more than 28 days (cumulative)). Previous therapy for Myelodysplastic Syndrome (MDS) is allowed.
4. Investigator considers patient ineligible for intensive remission induction therapy based on documented medical reasons (e.g. disease characteristics like AML genetics, type of AML (de novo or secondary), and patient characteristics like performance score, concomitant diagnoses, organ dysfunctions).
5. Patient is eligible for Low-Dose Cytarabine (LDAC) treatment.
6. Eastern co-operative oncology group (ECOG) performance score \<= 2 at screening.
7. Signed and dated written informed consent by start date of Screening visit in accordance with Good Clinical Practice (GCP) and local legislation.

Exclusion criteria:

1. Prior or concomitant chemotherapy for AML (with the exception of hydroxyurea and/or corticosteroid therapy for no more than 28 days (cumulative)). Please note that any prior therapy for MDS is allowed.
2. Treatment with any investigational drug within 2 weeks before first administration of present trial drug.
3. Acute promyelocytic leukaemia (French-American-British (FAB) classification subtype M3).
4. Current clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukaemic CNS involvement (no lumbar puncture required, clinical assessment per investigator´s judgement is sufficient).
5. Hypersensitivity to one of the trial drugs or the excipients.
6. Severe illness or organ dysfunction involving the heart, kidney, liver or other organ system (e.g. active infection, clinically relevant impairment of cardiac function, severe heart failure/cardiac insufficiency, unstable angina pectoris or history of recent myocardial infarction), which in the opinion of the investigator precludes treatment with LDAC.
7. Corrected QT interval according to Fridericia (QTcF) prolongation \> 470 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome).The QTcF will be calculated as the mean of the 3 Electrocardiogram (ECGs) taken at screening.
8. Total bilirubin \> 3 x upper limit of normal (ULN).
9. Creatinine clearance (CLcr) \< 30 ml/min (estimated creatinine clearance by the Cockcroft-Gault (C-G) equation) .
10. Active hepatitis B or hepatitis C, or laboratory evidence for a chronic infection.
11. HIV infection.
12. Second malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment e.g. in prostate or breast cancer).
13. Any significant concurrent psychiatric disorder or social situation that according to the investigator´s judgement would compromise patient´s safety or compliance, interfere with consent, study participation, or interpretation of study results.
14. Known or suspected active alcohol or drug abuse.
15. Patient unable to comply with the protocol, in the opinion of the investigator.
16. Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second medically acceptable method of contraception during the trial and for a minimum of 6 months after study treatment.

Primary outcomes:
measure: Objective Response (OR)
timeFrame: Response assessment was performed at the end of every 2nd cycle, (i.e. at the end of Cycle 2, 4, 6, 8, etc., and at end of treatment), i.e. up to 52 months.
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization until death due to any cause, up to 1557 days.
measure: Event-free Survival (EFS)
timeFrame: From randomization until disease progression or relapse or death from any cause, up to 1557 days.
measure: Relapse-free Survival (RFS)
timeFrame: From randomization until disease progression or relapse or death from any cause, up to 1557 days.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California
state: California
city: Duluth
country: United States
facility: St. Luke's Hospital Association of Duluth, Inc.
state: Minnesota
city: Nashville
country: United States
facility: Henry-Joyce Cancer Clinic
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Mendoza
country: Argentina
facility: Fundacion COIR
city: San Miguel de Tucumán
country: Argentina
facility: Hospital Central de Salud Zenón Santillan
city: Graz
country: Austria
facility: LKH-Univ. Hospital Graz
city: Leoben
country: Austria
facility: LKH Leoben
city: Wien
country: Austria
facility: Hospital Hietzing
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge
city: Bruxelles
country: Belgium
facility: Brussels - UNIV Saint-Luc
city: Haine-Saint-Paul
country: Belgium
facility: Haine-St-Paul - HOSP Jolimont
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis - Campus Virga Jesse
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
city: Roeselare
country: Belgium
facility: Roeselare - HOSP AZ Delta
city: Yvoir
country: Belgium
facility: Yvoir - UNIV UCL de Mont-Godinne
city: Jau
country: Brazil
facility: Hospital Doutor Amaral Carvalho
city: Porto Alegre
country: Brazil
facility: Hospital Mãe de Deus
city: Ribeirao Preto
country: Brazil
facility: H.C.da Fac. de Medicina de Ribeirao Preto
city: Edmonton
country: Canada
facility: University of Alberta Hospital (University of Alberta)
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Migration Data
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Montreal General Hospital - McGill University Health Centre
state: Quebec
city: Hradec Kralove
country: Czechia
facility: Hospital Hradec Kralove
city: Plzen - Lochotin
country: Czechia
facility: University Hospital Plzen, Plzen-Lochotin
city: Praha 10
country: Czechia
facility: Univ. Hospital Kralovske Vinohrady
city: Helsinki
country: Finland
facility: Meilahden sairaala
city: Turku
country: Finland
facility: TYKS, Sisätautien klinikka
city: Amiens
country: France
facility: HOP Amiens-Picardie Sud
city: Caen
country: France
facility: HOP Côte de Nacre
city: La Tronche
country: France
facility: HOP Michallon
city: Le Chesnay
country: France
facility: HOP André Mignot
city: Limoges Cedex 1
country: France
facility: HOP Dupuytren 1
city: Marseille
country: France
facility: INS Paoli-Calmettes
city: Nantes
country: France
facility: HOP Nantes, Hémato, Nantes
city: Paris Cedex 12
country: France
facility: HOP Saint-Antoine
city: Pessac
country: France
facility: HOP Haut-Lévêque
city: Pierre Bénite
country: France
facility: HOP Lyon Sud
city: Rennes Cedex 9
country: France
facility: HOP Pontchaillou
city: Toulouse
country: France
facility: INS Universitaire du Cancer
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg
city: Berlin
country: Germany
facility: Med. Klinik m.S. Hämatologie und Onkologie
city: Braunschweig
country: Germany
facility: Städtisches Klinikum Braunschweig gGmbH
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Essen
country: Germany
facility: Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
city: Frankfurt/Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen, Georg-August-Universität
city: Halle (Saale)
country: Germany
facility: Martin-Luther-Universität Halle-Wittenberg
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Kiel
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Marburg
country: Germany
facility: Universitätsklinikum Gießen und Marburg GmbH
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus GmbH
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum
city: Athens
country: Greece
facility: General Hospital of Athens "G. Gennimatas"
city: Athens
country: Greece
facility: General Hospital of Athens "Laiko"
city: Ioannina
country: Greece
facility: Univ. Gen. Hosp. of Ioannina
city: Patras
country: Greece
facility: University of Patras Medical School
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "G. Papanikolaou"
city: Budapest
country: Hungary
facility: Semmelweis University
city: Gyor
country: Hungary
facility: Petz Aldar Hospital, 2nd Dept. of Internal Med., Haematology
city: Szeged
country: Hungary
facility: Univ. of Szeged, 2nd Dept. of Internal Med., Haematology
city: Bangalore
country: India
facility: St. John Medical College and hospital
city: Mumbai
country: India
facility: Tata Memorial Hospital
city: Brescia
country: Italy
facility: A.O. Spedali Civili di Brescia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Torino
country: Italy
facility: AO Città della Salute e della
city: Aichi, Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center
city: Aichi, Nagoya
country: Japan
facility: Japanese Red Cross Nagoya Daini Hospital
city: Akita, Akita
country: Japan
facility: Akita University Hospital
city: Fukui, Yoshida-gun
country: Japan
facility: University of Fukui Hospital
city: Fukuoka, Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hyogo, Kobe
country: Japan
facility: Kobe University Hospital
city: Kanagawa, Isehara
country: Japan
facility: Tokai University Hospital
city: Kanagawa, Yokohama
country: Japan
facility: Yokohama City University Medical Center
city: Miyagi, Sendai
country: Japan
facility: Tohoku University Hospital
city: Nagasaki, Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Okayama, Kurashiki
country: Japan
facility: Kurashiki Central Hospital
city: Okayama, Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka, Osaka
country: Japan
facility: Osaka City University Hospital
city: Tokyo, Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Tokyo, Sinagawa-ku
country: Japan
facility: NTT Medical Center Tokyo
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St.Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr Jose Eleuterio Gonzalez
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC Locatie VUMC
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus
city: Grålum
country: Norway
facility: Sykehuset Østfold Kalnes
city: Lodz
country: Poland
facility: Reg. Specialist Hospital of M. Kopernik, Dept. Haematology
city: Torun
country: Poland
facility: City Hospital Torun, Department of Hematology
city: Lisboa
country: Portugal
facility: CHULN, EPE - Hospital de Santa Maria
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário do Porto, EPE - Hospital de Santo António
city: Porto
country: Portugal
facility: IPO Porto Francisco Gentil, EPE
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário São João,EPE
city: Irkutsk
country: Russian Federation
facility: Regional Clinical Hospital 'The Badge of Honor Order'
city: Moscow
country: Russian Federation
facility: FSBI "N.N Blokhin Med.Res.Cent.Onc."MoH of RF
city: Nizhniy Novgorod
country: Russian Federation
facility: Nizhniy Novgorod Reg. Clinical Hospital, Dept. Haematology
city: St. Petersburg
country: Russian Federation
facility: Leningrad Reg. Clin. Hosp., Oncohematology Department No. 2
city: Moreleta Park, Pretoria
country: South Africa
facility: Netcare Pretoria East Hospital
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital La Paz
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital Politècnic La Fe
city: ChangHua
country: Taiwan
facility: Chang-Hua Christian Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Hagege A, Ambrosetti D, Boyer J, Bozec A, Doyen J, Chamorey E, He X, Bourget I, Rousset J, Saada E, Rastoin O, Parola J, Luciano F, Cao Y, Pages G, Dufies M. The Polo-like kinase 1 inhibitor onvansertib represents a relevant treatment for head and neck squamous cell carcinoma resistant to cisplatin and radiotherapy. Theranostics. 2021 Sep 21;11(19):9571-9586. doi: 10.7150/thno.61711. eCollection 2021.