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

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ClinicalTrials.gov Identifier: NCT00804856
Recruitment Status : Active, not recruiting
First Posted : December 9, 2008
Last Update Posted : April 11, 2019
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE September 18, 2008
First Posted Date  ICMJE December 9, 2008
Last Update Posted Date April 11, 2019
Actual Study Start Date  ICMJE November 27, 2008
Actual Primary Completion Date March 9, 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2016)
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 8, 2008)
Phase I part: MTD of BI 6727 monotherapy and BI 6727 in combination with LDAraC Phase IIa part: Efficacy [ Time Frame: 21 months ]
Change History Complete list of historical versions of study NCT00804856 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2016)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2008)
Incidence and intensity of AEs; Incidence of DLT; PK; PD; PR; EFS; RFS; Remission duration;OS; QTc changes; Supportive care req. [ Time Frame: 36 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I/IIa Trial to Investigate BI 6727 (Volasertib) as Monotherapy or in Combination With Cytarabine in Acute Myeloid Leukaemia
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia, Myeloid, Acute
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • Experimental: Schedule A
    BI 6727 (d1 and 15 - one hour iv.) + LD ARA C 2x20 mg/d s.c.
    Interventions:
    • Drug: BI 6727 (d1 and 15)
    • Drug: Cytarabine
  • Experimental: Schedule B
    BI 6727 (d1 and 15 - one hour iv.)
    Intervention: Drug: BI 6727 (d1 and 15)
  • Active Comparator: Schedule C
    LD-ARA C monotherapy (2 x 20 mg/d s.c.)
    Intervention: Drug: Cytarabine
Publications * Döhner H, Lübbert M, Fiedler W, Fouillard L, Haaland A, Brandwein JM, Lepretre S, Reman O, Turlure P, Ottmann OG, Müller-Tidow C, Krämer A, Raffoux E, Döhner K, Schlenk RF, Voss F, Taube T, Fritsch H, Maertens J. Randomized, phase 2 trial of low-dose cytarabine with or without volasertib in AML patients not suitable for induction therapy. Blood. 2014 Aug 28;124(9):1426-33. doi: 10.1182/blood-2014-03-560557. Epub 2014 Jul 8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 29, 2013)
180
Original Estimated Enrollment  ICMJE
 (submitted: December 8, 2008)
145
Estimated Study Completion Date  ICMJE November 18, 2019
Actual Primary Completion Date March 9, 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Belgium,   Canada,   France,   Germany,   Italy,   Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00804856
Other Study ID Numbers  ICMJE 1230.4
2008-003617-27 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account Boehringer Ingelheim
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP