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)

Leukemia, Myeloid, Acute Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01721876
• Other study ID #: 1230.14
• Secondary ID: 2012-002487-27
• Status: Completed
• Phase: Phase 3
• Start date: January 29, 2013
• Est. completion date: May 28, 2021

Study information

• Verified date: February 2023
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 666
• Est. completion date: May 28, 2021
• Est. primary completion date: August 12, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Placebo
Placebo matching Volasertib
• Volasertib
Volasertib
• Cytarabine
Cytarabine

Locations

Country	Name	City	State
Argentina	Fundacion COIR	Mendoza
Argentina	Hospital Central de Salud Zenón Santillan	San Miguel de Tucumán
Austria	LKH-Univ. Hospital Graz	Graz
Austria	LKH Leoben	Leoben
Austria	Hospital Hietzing	Wien
Belgium	AZ Sint-Jan Brugge	Brugge
Belgium	Brussels - UNIV Saint-Luc	Bruxelles
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
Brazil	Hospital Doutor Amaral Carvalho	Jau
Brazil	Hospital Mãe de Deus	Porto Alegre
Brazil	H.C.da Fac. de Medicina de Ribeirao Preto	Ribeirao Preto
Canada	University of Alberta Hospital (University of Alberta)	Edmonton	Alberta
Canada	Maisonneuve-Rosemont Hospital	Montreal	Migration Data
Canada	Montreal General Hospital - McGill University Health Centre	Montreal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Czechia	Hospital Hradec Kralove	Hradec Kralove
Czechia	University Hospital Plzen, Plzen-Lochotin	Plzen - Lochotin
Czechia	Univ. Hospital Kralovske Vinohrady	Praha 10
Finland	Meilahden sairaala	Helsinki
Finland	TYKS, Sisätautien klinikka	Turku
France	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 Cedex 1
France	INS Paoli-Calmettes	Marseille
France	HOP Nantes, Hémato, Nantes	Nantes
France	HOP Saint-Antoine	Paris Cedex 12
France	HOP Haut-Lévêque	Pessac
France	HOP Lyon Sud	Pierre Bénite
France	HOP Pontchaillou	Rennes Cedex 9
France	INS Universitaire du Cancer	Toulouse
Germany	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/Main
Germany	Universitätsmedizin Göttingen, Georg-August-Universität	Göttingen
Germany	Martin-Luther-Universität Halle-Wittenberg	Halle (Saale)
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
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
Greece	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	Patras
Greece	General Hospital of Thessaloniki "G. Papanikolaou"	Thessaloniki
Hungary	Semmelweis University	Budapest
Hungary	Petz Aldar Hospital, 2nd Dept. of Internal Med., Haematology	Gyor
Hungary	Univ. of Szeged, 2nd Dept. of Internal Med., Haematology	Szeged
India	St. John Medical College and hospital	Bangalore
India	Tata Memorial Hospital	Mumbai
Italy	A.O. Spedali Civili di Brescia	Brescia
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	AO Città della Salute e della	Torino
Japan	Japanese Red Cross Nagoya Daini Hospital	Aichi, Nagoya
Japan	National Hospital Organization Nagoya Medical Center	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
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St.Mary's Hospital	Seoul
Mexico	Hospital Universitario Dr Jose Eleuterio Gonzalez	Monterrey
Netherlands	Amsterdam UMC Locatie VUMC	Amsterdam
Norway	Haukeland Universitetssykehus	Bergen
Norway	Sykehuset Østfold Kalnes	Grålum
Poland	Reg. Specialist Hospital of M. Kopernik, Dept. Haematology	Lodz
Poland	City Hospital Torun, Department of Hematology	Torun
Portugal	CHULN, EPE - Hospital de Santa Maria	Lisboa
Portugal	Centro Hospitalar Universitário do Porto, EPE - Hospital de Santo António	Porto
Portugal	Centro Hospitalar Universitário São João,EPE	Porto
Portugal	IPO Porto Francisco Gentil, EPE	Porto
Russian Federation	Regional Clinical Hospital 'The Badge of Honor Order'	Irkutsk
Russian Federation	FSBI "N.N Blokhin Med.Res.Cent.Onc."MoH of RF	Moscow
Russian Federation	Nizhniy Novgorod Reg. Clinical Hospital, Dept. Haematology	Nizhniy Novgorod
Russian Federation	Leningrad Reg. Clin. Hosp., Oncohematology Department No. 2	St. Petersburg
South Africa	Netcare Pretoria East Hospital	Moreleta Park, Pretoria
Spain	Hospital Germans Trias i Pujol	Badalona
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital La Paz	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Politècnic La Fe	Valencia
Taiwan	Chang-Hua Christian Hospital	ChangHua
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
United States	St. Luke's Hospital Association of Duluth, Inc.	Duluth	Minnesota
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of California	Los Angeles	California
United States	Henry-Joyce Cancer Clinic	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Brazil,  Canada,  Czechia,  Finland,  France,  Germany,  Greece,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Russian Federation,  South Africa,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response (OR)	OR is the number of patients who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi), where OR was based on the best response attained during the treatment period.	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	Overall Survival (OS)	OS is the key secondary endpoint and was measured from the date of randomization until death from any cause. Patients who were lost to follow-up were censored on the last date they were known to be alive.	From randomization until death due to any cause, up to 1557 days.
Secondary	Event-free Survival (EFS)	EFS was measured from the date of randomisation to the date of progression or relapse, or death from any cause, whichever occurred first.	From randomization until disease progression or relapse or death from any cause, up to 1557 days.
Secondary	Relapse-free Survival (RFS)	RFS was defined only for patients who achieved best overall response of CR or CRi; it was measured from the date of achievement of a remission until the date of relapse or death from any cause. Patients not known to have relapsed or died at last follow-up were censored on the date they were last examined.	From randomization until disease progression or relapse or death from any cause, up to 1557 days.

External Links

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