Phase I/IIa Trial to Investigate BI 6727 (Volasertib) as Monotherapy or in Combination With Cytarabine in Acute Myeloid Leukaemia
Leukemia, Myeloid, Acute
About this trial
This is an interventional treatment trial for Leukemia, Myeloid, Acute
Eligibility Criteria
Inclusion criteria:
Male or female adult with relapsed/refractory AML ineligible for intensive treatment (phase I part only) Male or female adult with previously untreated AML ineligible for intensive treatment (phase IIa part only) Confirmed diagnosis of AML according to the WHO definition (except for acute promyelocytic leukaemia, APL) Patient is eligible for LD-Ara-C treatment Life expectancy > 3 months Eastern co-operative oncology group (ECOG, R01-0787) performance score <=2 at screening Signed written informed consent consistent with international conference on harmonisation, good clinical practice (ICH-GCP) and local legislation
Exclusion criteria:
Previously untreated AML (phase I part only) Relapsed or treatment refractory AML (phase IIa part only) Patient with APL (AML subtype M3 according to the French-American-British (FAB) classification) Hypersensitivity to one of the trial drugs or the excipients Other malignancy requiring treatment Symptomatic central nervous system involvement Clinically relevant QT prolongation (e.g. long QT syndrome, QTcF>470 ms) Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (ULN), or AST or ALT greater than 5 times the ULN in case of known leukaemia liver involvement Prothrombin time (PT) > 1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin) Bilirubin greater than 1.5 mg/dl (> 26 mcmol/L) Serum creatinine greater than 2.0 mg/dl Concomitant intercurrent illness, which would compromise the evaluation of efficacy or safety of the trial drug, e.g. active severe infection, unstable angina pectoris, cardiac arrhythmia or severe heart failure/cardiac insufficiency.
Psychiatric illness or social situation that would limit compliance with trial requirements Concomitant therapy, which is considered relevant for the evaluation of the efficacy or safety of the trial drug Contraindications for cytarabine treatment according to the SPC Female patients of childbearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial, i.e. combination of two forms of effective contraception (hormonal contraception, intrauterine device, condom with spermicide, etc.).
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 Pregnant or nursing female patients Patient unable to comply with the protocol
Sites / Locations
- LKH-Univ. Hospital Graz
- AZ Sint-Jan Brugge
- Brussels - UNIV Saint-Luc
- UZ Leuven
- Princess Margaret Cancer Centre
- Montreal General Hospital - McGill University Health Centre
- CHUS Fleurimont
- HOP Clémenceau, Hémato, Caen
- HOP, Centre Hospitalier René Dubos, Hémato, Paris
- HOP Dupuytren 1
- HOP Edouard Herriot
- CTR, fondation Paschetta, Hémato, Nice
- HOP Saint-Louis
- CTR Henri Becquerel
- Campus Virchow-Klinikum, Berlin
- Universitätsklinikum Frankfurt
- Universitätsklinikum Freiburg
- Universitätsklinikum Hamburg-Eppendorf
- Universitätsklinikum Heidelberg
- Universitätsklinikum Schleswig-Holstein, Campus Kiel
- Universitätsklinikum Münster
- Universitätsklinikum Ulm
- A.O. Spedali Civili di Brescia
- ASST Grande Ospedale Metropolitano Niguarda
- Azienda Ospedaliera Policlinico di Modena
- Haukeland Universitetssykehus
- Oslo Universitetssykehus HF, Ullevål sykehus
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Arm 14
Arm 15
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Active Comparator
Experimental
Phase I Schedule A. Volasertib 150 mg+LDAC
Phase I Schedule A. Volasertib 200 mg+LDAC
Phase I Schedule A. Volasertib 250 mg+LDAC
Phase I Schedule A. Volasertib 300 mg+LDAC
Phase I Schedule A. Volasertib 350 mg+LDAC
Phase I Schedule A. Volasertib 400 mg+LDAC
Phase I Schedule B. Volasertib 150 mg
Phase I Schedule B. Volasertib 200 mg
Phase I Schedule B. Volasertib 350 mg
Phase I Schedule B. Volasertib 400 mg
Phase I Schedule B. Volasertib 450 mg
Phase I Schedule B. Volasertib 500 mg
Phase I Schedule B. Volasertib 550 mg
Phase II Schedule C. LDAC
Phase II Schedule A. Volasertib 350 mg+LDAC
Volasertib 150 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.
Volasertib 200 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.
Volasertib 250 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.
Volasertib 300 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.
Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.
Volasertib 400 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.
Volasertib 150 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).
Volasertib 200 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).
Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).
Volasertib 400 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).
Volasertib 450 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).
Volasertib 500 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).
Volasertib 550 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).
Low-dose cytarabine (LDAC) monotherapy 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 days treatment cycle.
Volasertib 350 milligram (mg) on Days 1 and 15 (28-day cycle) administered by Intravenous Infusion (IV) over 60 minutes and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 days treatment cycle.