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)

NCT ID: NCT01721876

Last Updated: 2023-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 666 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-29
• Study Completion Date: 2021-05-28

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

Conditions

Leukemia, Myeloid, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Volasertib and Cytarabine

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

Volasertib

Cytarabine

Intervention Type: DRUG

Cytarabine

Placebo and Cytarabine

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matching Volasertib

Cytarabine

Intervention Type: DRUG

Cytarabine

Interventions

Placebo

Placebo matching Volasertib

Intervention Type: DRUG

Volasertib

Volasertib

Intervention Type: DRUG

Cytarabine

Cytarabine

Intervention Type: DRUG

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.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

University of California

Los Angeles, California, United States

St. Luke's Hospital Association of Duluth, Inc.

Duluth, Minnesota, United States

Henry-Joyce Cancer Clinic

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Fundacion COIR

Mendoza, , Argentina

Hospital Central de Salud Zenón Santillan

San Miguel de Tucumán, , Argentina

LKH-Univ. Hospital Graz

Graz, , Austria

LKH Leoben

Leoben, , Austria

Hospital Hietzing

Vienna, , Austria

AZ Sint-Jan Brugge

Bruges, , Belgium

Brussels - UNIV Saint-Luc

Brussels, , Belgium

Haine-St-Paul - HOSP Jolimont

Haine-Saint-Paul, , Belgium

Jessa Ziekenhuis - Campus Virga Jesse

Hasselt, , Belgium

UZ Leuven

Leuven, , Belgium

Centre Hospitalier Universitaire de Liège

Liège, , Belgium

Roeselare - HOSP AZ Delta

Roeselare, , Belgium

Yvoir - UNIV UCL de Mont-Godinne

Yvoir, , Belgium

Hospital Doutor Amaral Carvalho

Jaú, , Brazil

Hospital Mãe de Deus

Porto Alegre, , Brazil

H.C.da Fac. de Medicina de Ribeirao Preto

Ribeirão Preto, , Brazil

University of Alberta Hospital (University of Alberta)

Edmonton, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

Maisonneuve-Rosemont Hospital

Montreal, Migration Data, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Montreal General Hospital - McGill University Health Centre

Montreal, Quebec, Canada

Hospital Hradec Kralove

Hradec Králové, , Czechia

University Hospital Plzen, Plzen-Lochotin

Plzen - Lochotin, , Czechia

Univ. Hospital Kralovske Vinohrady

Prague, , Czechia

Meilahden sairaala

Helsinki, , Finland

TYKS, Sisätautien klinikka

Turku, , Finland

HOP Amiens-Picardie Sud

Amiens, , France

HOP Côte de Nacre

Caen, , France

HOP Michallon

La Tronche, , France

HOP André Mignot

Le Chesnay, , France

HOP Dupuytren 1

Limoges, , France

INS Paoli-Calmettes

Marseille, , France

HOP Nantes, Hémato, Nantes

Nantes, , France

HOP Saint-Antoine

Paris, , France

HOP Haut-Lévêque

Pessac, , France

HOP Lyon Sud

Pierre-Bénite, , France

HOP Pontchaillou

Rennes, , France

INS Universitaire du Cancer

Toulouse, , France

Universitätsklinikum Augsburg

Augsburg, , Germany

Med. Klinik m.S. Hämatologie und Onkologie

Berlin, , Germany

Städtisches Klinikum Braunschweig gGmbH

Braunschweig, , Germany

Universitätsklinikum Erlangen

Erlangen, , Germany

Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH

Essen, , Germany

Universitätsklinikum Frankfurt

Frankfurt am Main, , Germany

Universitätsmedizin Göttingen, Georg-August-Universität

Göttingen, , Germany

Martin-Luther-Universität Halle-Wittenberg

Halle, , Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Universitätsklinikum Schleswig-Holstein, Campus Kiel

Kiel, , Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, , Germany

Universitätsklinikum Gießen und Marburg GmbH

Marburg, , Germany

Klinikum rechts der Isar der Technischen Universität München

München, , Germany

Universitätsklinikum Münster

Münster, , Germany

Universitätsklinikum Regensburg

Regensburg, , Germany

Robert-Bosch-Krankenhaus GmbH

Stuttgart, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Schwarzwald-Baar Klinikum

Villingen-Schwenningen, , Germany

General Hospital of Athens "G. Gennimatas"

Athens, , Greece

General Hospital of Athens "Laiko"

Athens, , Greece

Univ. Gen. Hosp. of Ioannina

Ioannina, , Greece

University of Patras Medical School

Pátrai, , Greece

General Hospital of Thessaloniki "G. Papanikolaou"

Thessaloniki, , Greece

Semmelweis University

Budapest, , Hungary

Petz Aldar Hospital, 2nd Dept. of Internal Med., Haematology

Győr, , Hungary

Univ. of Szeged, 2nd Dept. of Internal Med., Haematology

Szeged, , Hungary

St. John Medical College and hospital

Bangalore, , India

Tata Memorial Hospital

Mumbai, , India

A.O. Spedali Civili di Brescia

Brescia, , Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

AO Città della Salute e della

Torino, , Italy

National Hospital Organization Nagoya Medical Center

Aichi, Nagoya, , Japan

Japanese Red Cross Nagoya Daini Hospital

Aichi, Nagoya, , Japan

Akita University Hospital

Akita, Akita, , Japan

University of Fukui Hospital

Fukui, Yoshida-gun, , Japan

Kyushu University Hospital

Fukuoka, Fukuoka, , Japan

Kobe University Hospital

Hyogo, Kobe, , Japan

Tokai University Hospital

Kanagawa, Isehara, , Japan

Yokohama City University Medical Center

Kanagawa, Yokohama, , Japan

Tohoku University Hospital

Miyagi, Sendai, , Japan

Nagasaki University Hospital

Nagasaki, Nagasaki, , Japan

Kurashiki Central Hospital

Okayama, Kurashiki, , Japan

Okayama University Hospital

Okayama, Okayama, , Japan

Osaka City University Hospital

Osaka, Osaka, , Japan

National Cancer Center Hospital

Tokyo, Chuo-ku, , Japan

NTT Medical Center Tokyo

Tokyo, Sinagawa-ku, , Japan

Hospital Universitario Dr Jose Eleuterio Gonzalez

Monterrey, , Mexico

Amsterdam UMC Locatie VUMC

Amsterdam, , Netherlands

Haukeland Universitetssykehus

Bergen, , Norway

Sykehuset Østfold Kalnes

Grålum, , Norway

Reg. Specialist Hospital of M. Kopernik, Dept. Haematology

Lodz, , Poland

City Hospital Torun, Department of Hematology

Torun, , Poland

CHULN, EPE - Hospital de Santa Maria

Lisbon, , Portugal

Centro Hospitalar Universitário do Porto, EPE - Hospital de Santo António

Porto, , Portugal

IPO Porto Francisco Gentil, EPE

Porto, , Portugal

Centro Hospitalar Universitário São João,EPE

Porto, , Portugal

Regional Clinical Hospital 'The Badge of Honor Order'

Irkutsk, , Russia

FSBI "N.N Blokhin Med.Res.Cent.Onc."MoH of RF

Moscow, , Russia

Nizhniy Novgorod Reg. Clinical Hospital, Dept. Haematology

Nizhny Novgorod, , Russia

Leningrad Reg. Clin. Hosp., Oncohematology Department No. 2

Saint Petersburg, , Russia

Netcare Pretoria East Hospital

Moreleta Park, Pretoria, , South Africa

Chonnam National University Hwasun Hospital

Hwasun, , South Korea

The Catholic University of Korea, Seoul St.Mary's Hospital

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Hospital Germans Trias i Pujol

Badalona, , Spain

Hospital Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Clínic de Barcelona

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital La Paz

Madrid, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital Politècnic La Fe

Valencia, , Spain

Chang-Hua Christian Hospital

Changhua, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Mackay Memorial Hospital

Taipei, , Taiwan

Countries

United States; Argentina; Austria; Belgium; Brazil; Canada; Czechia; Finland; France; Germany; Greece; Hungary; India; Italy; Japan; Mexico; Netherlands; Norway; Poland; Portugal; Russia; South Africa; South Korea; Spain; Taiwan

References

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.

Reference Type: DERIVED

PMID: 34646387 (View on PubMed)

Related Links

http://www.mystudywindow.com/

Related Info

Other Identifiers

2012-002487-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1230.14

Identifier Type: -

Identifier Source: org_study_id