Clinical trial NCT00632749: BI 811283 in Combination With Cytarabine in Previously Untreated AML Ineligible for Intensive Treatment
Official title: An Open Phase I/IIa Trial to Investigate the Maximum Tolerated Dose, Safety, Efficacy and Pharmacokinetics of BI 811283 in Combination With Cytarabine in Patients With Previously Untreated Acute Myeloid Leukaemia Ineligible for Intensive Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Myeloid, Acute
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-03-11
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Investigation of maximum tolerated dose, safety, efficacy and pharmcokinetics of BI 811283 in combination with cytarabine (LD-Ara-C) in previously untreated acute myeloid leukaemia (AML) patients


Eligibility criteria: Inclusion criteria:

* Male or female adult with previously untreated acute myeloid leukaemia (AML)
* Confirmed diagnosis of AML according to the WHO definition (except for acute promyelocytic leukaemia, APL)
* Patient is considered ineligible for intensive treatment
* Patient is eligible for low-dose cytarabine (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:

* Patient with APL (AML subtype M3 according to the French-American-British (FAB) classification).
* Relapsed or treatment refractory AML.
* Hypersensitivity to one of the trial drugs or the excipients.
* Other malignancy requiring treatment.
* Known central nervous system involvement.
* Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (ULN).
* INR \> 1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin).
* Bilirubin greater than 1.5 mg/dl.
* Serum creatinine greater than 2.0 mg/dl.
* LVEF (Left ventricular ejection fraction) \< 50% in echocardiography or clinical congestive heart failure New York Heart Association (NYHA) grade III or IV.
* Concomitant intercurrent illness, which would compromise the evaluation of efficacy or safety of the trial drug, e.g. active severe infection, unstable angina pectoris or cardiac arrhythmia.
* 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 (i.e. other chemo- or immunotherapy, see also section 4.2.2).
* Contraindications for cytarabine treatment according to the summary of product characteristics (SPC).
* Patients who are sexually active and unwilling to use a medically acceptable method of contraception during the trial (hormonal contraception, intrauterine device, condom with spermicide, etc.).
* Pregnant or nursing female patients.
* Patient unable to comply with the protocol.

Primary outcomes:
measure: The Maximum Tolerated Dose (MTD) of 2 Schedules of BI 811283 in Combination With Cytarabine.
timeFrame: up to 28 days of treatment
Secondary outcomes:
measure: Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi])
timeFrame: Data collected up to cut-off date 20Oct2011, Up to 1239 days
measure: Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0)
timeFrame: Data from first treatment administration until cut-off date of 20 October 2011; up to 1239 days
measure: Incidence of Dose Limiting Toxicity (DLT)
timeFrame: up to 28 days of treatment
measure: Partial Remission
timeFrame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
measure: Event Free Survival (EFS)
timeFrame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
measure: Relapse Free Survival
timeFrame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
measure: Remission Duration
timeFrame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
measure: Overall Survival (OS)
timeFrame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days
measure: Cmax (Maximum Measured Concentration of BI 811283 in Plasma)
timeFrame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
measure: AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
timeFrame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
measure: AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point)
timeFrame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
measure: Cmax,ss (Maximum Measured Concentration of BI 811283 in Plasma at Steady State)
timeFrame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
measure: AUC (0-inf, ss)(Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) at Steady State
timeFrame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
measure: AUC (0-tz,ss) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) at Steady State
timeFrame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
measure: Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma)
timeFrame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
measure: Tmax,ss (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma at Steady State)
timeFrame: -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283
measure: Cmax (Maximum Measured Concentration of Cytarabine in Plasma)
timeFrame: -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine
measure: Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma)
timeFrame: -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine
measure: AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
timeFrame: -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine
measure: AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point)
timeFrame: -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine
measure: Pharmacodynamic Monitoring
timeFrame: On Day 5, i.e. 72 hours after the end of the first BI 811283 infusion, and on Day 28 in the first cycle only
measure: Pharmacokinetics of Cytarabine After a Single Dose and at Steady State When Given Alone
timeFrame: -0.05, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: 1247.3.49007 Boehringer Ingelheim Investigational Site
city: Frankfurt/Main
country: Germany
facility: 1247.3.49005 Boehringer Ingelheim Investigational Site
city: Freiburg
country: Germany
facility: 1247.3.49004 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1247.3.49006 Boehringer Ingelheim Investigational Site
city: Heidelberg
country: Germany
facility: 1247.3.49003 Boehringer Ingelheim Investigational Site
city: Münster
country: Germany
facility: 1247.3.49002 Boehringer Ingelheim Investigational Site
city: Ulm
country: Germany
facility: 1247.3.49001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Dohner H, Muller-Tidow C, Lubbert M, Fiedler W, Kramer A, Westermann J, Bug G, Schlenk RF, Krug U, Goeldner RG, Hilbert J, Taube T, Ottmann OG. A phase I trial investigating the Aurora B kinase inhibitor BI 811283 in combination with cytarabine in patients with acute myeloid leukaemia. Br J Haematol. 2019 May;185(3):583-587. doi: 10.1111/bjh.15563. Epub 2018 Nov 19. No abstract available.