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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.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00804856
First Posted: December 9, 2008
Last Update Posted: August 28, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Boehringer Ingelheim
  Purpose
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
Intervention Model: Parallel Assignment
Masking: None (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 ]
  • Phase IIa part: Efficacy (complete remission, CR; complete remission with incomplete blood count recovery, CRi) [ Time Frame: minimum 4 weeks, maximum LPO ]

Secondary Outcome Measures:
  • Incidence and intensity of adverse events graded according to CTCAE (version 3.0) [ Time Frame: minimum 4 weeks, maximum LPO ]
  • Incidence of dose limiting toxicity (DLT) [ Time Frame: minimum 4 weeks, maximum LPO ]
  • Pharmacodynamic monitoring: drug effect on leukaemia cells [ Time Frame: 4 weeks ]
  • Partial remission (PR) [ Time Frame: minimum 4 weeks, maximum LPO ]
  • Event free survival (EFS) [ Time Frame: minimum 4 weeks, maximum LPO ]
  • Relapse free survival [ Time Frame: minimum 4 weeks, maximum LPO ]
  • Remission duration [ Time Frame: minimum 4 weeks, maximum LPO ]
  • Overall survival (OS) [ Time Frame: minimum 4 weeks, maximum LPO ]
  • QTc changes during and after intravenous infusion of BI 6727 [ Time Frame: minimum 4 weeks, maximum LPO ]
  • Supportive care requirements (blood products, antibiotic usage, hospitalisation) [ Time Frame: minimum 4 weeks, maximum LPO ]
  • Pharmacokinetics of BI 6727 when given alone and in combination with cytarabine: CL (Total Clearance of Volasertib in Plasma after i.v-Intravenous Administration) of BI 6727 [ Time Frame: minimum 4 weeks, maximum 8 weeks ]
  • Pharmacokinetics of cytarabine after a single dose when given alone and in combination with BI 6727: Cmax, norm: dose normalized maximum measured concentration of cytarabine in plasma [ Time Frame: minimum 4 weeks, maximum 8 weeks ]
  • Pharmacokinetics of cytarabine after a single dose when given alone and in combination with BI 6727: dose normalized area under the concentration-time curve of cytarabine in plasma over the time interval from 0 extrapolated up to 4 hours [ Time Frame: minimum 4 weeks, maximum 8 weeks ]
  • Pharmacokinetics of BI 6727 when given alone and in combination with cytarabine: VSS (Apparent Volume of Distribution at Steady State Following i.v.) of BI 6727 [ Time Frame: minimum 4 weeks, maximum 8 weeks ]

Enrollment: 180
Actual Study Start Date: November 27, 2008
Estimated Study Completion Date: January 11, 2018
Primary Completion Date: March 9, 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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00804856


Locations
Belgium
Brussels - UNIV St-Luc
Bruxelles, Belgium, 1200
UZ Leuven
Leuven, Belgium, 3000
Canada, Migration Data
Montreal General Hospital - McGill University Health Centre
Montreal, Migration Data, Canada, H3G 1A4
France
HOP, Centre Hospitalier René Dubos, Hémato, Paris
Cergy Pontoise Cedex, France, 95303
HOP, Hôpital Dupuytren, Hémato, Limoges
Limoges, France, 87042
Germany
Universitätsklinikum Frankfurt
Frankfurt/Main, Germany, 60590
II. Medizinische Klinik und Poliklinik
Hamburg, Germany, 20246
Norway
Haukeland Universitetssykehus
Bergen, Norway, N-5021
Oslo Universitetssykehus HF, Ullevål sykehus
Oslo, Norway, N-0450
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00804856     History of Changes
Other Study ID Numbers: 1230.4
2008-003617-27 ( EudraCT Number )
First Submitted: September 18, 2008
First Posted: December 9, 2008
Last Update Posted: August 28, 2017
Last Verified: August 2017

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs