Phase I/IIa Trial to Investigate BI 6727 (Volasertib) as Monotherapy or in Combination With Cytarabine in Acute Myeloid Leukaemia

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Boehringer Ingelheim Identifier:
First received: September 18, 2008
Last updated: October 1, 2015
Last verified: October 2015
The trial will be performed in two parts, a phase I part and a phase IIa part. In the phase I part of the trial, BI 6727 will be investigated as monotherapy and in combination with low dose cytarabine (LD-Ara-C) in patients with relapsed/refractory AML that are not eligible for intensive treatment. The dose of BI 6727 will be escalated to determine the maximum tolerated dose (MTD) of BI 6727 monotherapy and BI 6727 in combination with LD-Ara-C in AML patients. In the phase IIa part, the combination of BI 6727 at MTD with LD-Ara-C and LD-Ara-C monotherapy will be investigated to explore the efficacy of the combination schedule in comparison to LD-Ara-C monotherapy in previously untreated AML patients that are not eligible for intensive treatment.

Condition Intervention Phase
Leukemia, Myeloid, Acute
Drug: BI 6727 (d1 and 15)
Drug: Cytarabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Phase I/IIa Trial to Investigate the Maximum Tolerated Dose, Safety, Pharmacokinetics, and Efficacy of Intravenous BI 6727 as Monotherapy or in Combination With Subcutaneous Cytarabine in Patients With Acute Myeloid Leukaemia

Resource links provided by NLM:

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Phase I part: MTD of BI 6727 monotherapy and BI 6727 in combination with LDAraC [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Phase IIa part: Efficacy (complete remission, CR; complete remission with incomplete blood count recovery, CRi) [ Time Frame: minimum 4 weeks, maximum n.a. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence and intensity of adverse events graded according to CTCAE (version 3.0) [ Time Frame: minimum 4 weeks, maximum n.a. ] [ Designated as safety issue: No ]
  • Incidence of dose limiting toxicity (DLT) [ Time Frame: minimum 4 weeks, maximum n.a. ] [ Designated as safety issue: No ]
  • Pharmacokinetics of BI 6727 when given alone and in combination with cytarabine [ Time Frame: minimum 4 weeks, maximum 8 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics of cytarabine after a single dose when given alone and in combination with BI 6727 [ Time Frame: minimum 4 weeks, maximum 8 weeks ] [ Designated as safety issue: No ]
  • Pharmacodynamic monitoring: drug effect on leukaemia cells [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Partial remission (PR) [ Time Frame: minimum 4 weeks, maximum n.a. ] [ Designated as safety issue: No ]
  • Event free survival (EFS) [ Time Frame: minimum 4 weeks, maximum n.a. ] [ Designated as safety issue: No ]
  • Relapse free survival [ Time Frame: minimum 4 weeks, maximum n.a. ] [ Designated as safety issue: No ]
  • Remission duration [ Time Frame: minimum 4 weeks, maximum n.a. ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: minimum 4 weeks, maximum n.a. ] [ Designated as safety issue: No ]
  • QTc changes during and after intravenous infusion of BI 6727 [ Time Frame: minimum 4 weeks, maximum n.a. ] [ Designated as safety issue: Yes ]
  • Supportive care requirements (blood products, antibiotic usage, hospitalisation) [ Time Frame: minimum 4 weeks, maximum n.a. ] [ Designated as safety issue: No ]

Enrollment: 180
Study Start Date: November 2008
Estimated Study Completion Date: January 2016
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Schedule A
BI 6727 (d1 and 15 - one hour iv.) + LD ARA C 2x20 mg/d s.c.
Drug: BI 6727 (d1 and 15)
BI 6727 (d1 and 15 - one hour iv.v)
Drug: Cytarabine
Cytarabine 2 x 20 mg/d s.c.
Experimental: Schedule B
BI 6727 (d1 and 15 - one hour iv.)
Drug: BI 6727 (d1 and 15)
BI 6727 (d1 and 15 - one hour iv.v)
Active Comparator: Schedule C
LD-ARA C monotherapy (2 x 20 mg/d s.c.)
Drug: Cytarabine
Cytarabine 2 x 20 mg/d s.c.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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

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Please refer to this study by its identifier: NCT00804856

1230.4.43001 Boehringer Ingelheim Investigational Site
Graz, Austria
1230.4.32003 Boehringer Ingelheim Investigational Site
Brugge, Belgium
1230.4.32001 Boehringer Ingelheim Investigational Site
Bruxelles, Belgium
1230.4.32002 Boehringer Ingelheim Investigational Site
Leuven, Belgium
Canada, Ontario
1230.4.1001 Boehringer Ingelheim Investigational Site
Toronto, Ontario, Canada
Canada, Quebec
1230.4.1002 Boehringer Ingelheim Investigational Site
Montreal, Quebec, Canada
1230.4.1003 Boehringer Ingelheim Investigational Site
Sherbrooke, Quebec, Canada
1230.4.3303A Boehringer Ingelheim Investigational Site
Caen, France
1230.4.3310A Boehringer Ingelheim Investigational Site
Cergy Pontoise Cedex, France
1230.4.3306A Boehringer Ingelheim Investigational Site
Limoges, France
1230.4.3307A Boehringer Ingelheim Investigational Site
Lyon Cedex 03, France
1230.4.3308A Boehringer Ingelheim Investigational Site
Nice Cedex 2, France
1230.4.3301A Boehringer Ingelheim Investigational Site
Paris cedex 10, France
1230.4.3311A Boehringer Ingelheim Investigational Site
Rouen Cedex, France
1230.4.49006 Boehringer Ingelheim Investigational Site
Berlin, Germany
1230.4.49003 Boehringer Ingelheim Investigational Site
Frankfurt/Main, Germany
1230.4.49005 Boehringer Ingelheim Investigational Site
Freiburg, Germany
1230.4.49008 Boehringer Ingelheim Investigational Site
Hamburg, Germany
1230.4.49004 Boehringer Ingelheim Investigational Site
Heidelberg, Germany
1230.4.49007 Boehringer Ingelheim Investigational Site
Kiel, Germany
1230.4.49002 Boehringer Ingelheim Investigational Site
Münster, Germany
1230.4.49001 Boehringer Ingelheim Investigational Site
Ulm, Germany
1230.4.39002 Boehringer Ingelheim Investigational Site
Brescia, Italy
1230.4.39003 Boehringer Ingelheim Investigational Site
Milano, Italy
1230.4.47001 Boehringer Ingelheim Investigational Site
Bergen, Norway
1230.4.47002 Boehringer Ingelheim Investigational Site
Oslo, Norway
Sponsors and Collaborators
Boehringer Ingelheim
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim Identifier: NCT00804856     History of Changes
Other Study ID Numbers: 1230.4  2008-003617-27 
Study First Received: September 18, 2008
Last Updated: October 1, 2015
Health Authority: Austria: Medicines and Medical Devices Agency
Belgium: Federal Agency for Medicinal and Health Products
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte)
Italy: National Institute of Health
Norway: Norwegian Medicines Agency

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on February 11, 2016