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

Primary Purpose

Leukemia, Myeloid, Acute

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Volasertib

Cytarabine

About this trial

This is an interventional treatment trial for Leukemia, Myeloid, Acute

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

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

Arm Description

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.

Outcomes

Primary Outcome Measures

Phase I: Maximum Tolerated Dose (MTD) of Volasertib in Combination With LDAC (Schedule A) and Volasertib Monotherapy (Schedule B)

To determine the Maximum tolerated dose (MTD), dose escalation was conducted following the 3+3 design with de-escalation. The MTD was defined as the highest dose at which 6 patients had been treated and less than 2 patients experienced a Dose limiting toxicity (DLT) within the first cycle of treatment. The MTD was defined based on safety data from the first cycle only. DLT is defined as drug related Common terminology criteria for adverse events (CTCAE) grade ≥ 3 nonhaematological toxicity (excluding: untreated nausea, untreated vomiting, CTCAE grade 3 untreated diarrhoea, CTCAE grade 3 "febrile neutropenia" and CTCAE grade 3 "infection with grade 3 or 4 neutrophils"). In patients with complete remission with incomplete blood count recovery (CRi) or partial remission (PR), persistent CTCAE grade 4 neutropenia or thrombocytopenia until three weeks after the end of the treatment cycle will be regarded a DLT.

Phase II: Number of Patients With Objective Response (Complete Remission (CR) + Complete Remission With Incomplete Blood Count Recovery (CRi))

Phase II: Number of patients with Objective Response (Complete remission (CR) + Complete remission with incomplete blood count recovery (CRi)). Complete remission (CR): morphologically leukaemia-free state (i.e. bone marrow with <5% blasts by morphologic criteria and no Auer rods, no evidence of extramedullary leukaemia) and absolute neutrophil count ≥1,000/microliter (μL) and platelets >100,000/μL. Complete remission with incomplete blood count recovery ("incomplete" CR, CRi): all of the above criteria for CR were met except that neutrophils <1,000/μL or platelets <100,000/μL in the blood were not achieved.

Phase I: Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)

A DLT was defined as a drug related CTCAE (Common Toxicity Criteria for Adverse Events) Grade ≥3 non-haematological toxicity (excluding untreated nausea, untreated vomiting, Grade 3 untreated diarrhea, Grade 3 febrile neutropenia, and Grade 3 infection with Grade 3 or 4 neutrophils). In patients with CRi (Complete Remission with Incomplete Blood Count Recovery) or PR (Partial Remission), persistent Grade 4 neutropenia or thrombocytopenia for 3 weeks after the end of the treatment cycle was regarded as a DLT unless the respective Grade 4 cytopenia was preexistent. In patients who required platelet substitution to maintain a Grade <4 before treatment, a Grade 4 thrombocytopenia after treatment did not constitute a DLT.

Secondary Outcome Measures

Best Overall Response

CR CR+CRi Partial remission: CR except bone marrow (BM) contained ≥5% but <25% blasts (or ≤50% initial blasts), or <5% blasts in presence of Auer rods or abnormal morphology. No change: survived ≥7 days (d) after 1st cycle with persistent leukemia in last peripheral blood smear or BM, or with persistent extramedullary disease, without further deterioration due to leukemia or increase of blasts in BM or peripheral blood. Aplasia: survived ≥7d after 1st cycle, died whilst cytopenic, with last post-treatment BM result aplastic or hypoplastic and without leukemia blasts. Indeterminate: survived <7 d after 1st cycle or survived ≥7d after 1st cycle, died with no persistent leukemia in peripheral smear but no post-treatment BM examination or did not complete 1st cycle. Progressive disease: survived ≥7d after 1st cycle with increase of blast population in BM or peripheral blood or aggravation or new extramedullary disease or further deterioration or death due to leukemia.

Phase I: Number of Patients With Objective Response: Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR+CRi)

Phase I: Number of patients with Objective Response (Complete remission (CR) + Complete remission with incomplete blood count recovery (CRi)). Complete remission (CR): morphologically leukaemia-free state (i.e. bone marrow with <5% blasts by morphologic criteria and no Auer rods, no evidence of extramedullary leukaemia) and absolute neutrophil count ≥1,000/microliter (μL) and platelets >100,000/μL. Complete remission with incomplete blood count recovery ("incomplete" CR, CRi): all of the above criteria for CR were met except that neutrophils <1,000/μL or platelets <100,000/μL in the blood were not achieved.

Phase II: Event Free Survival

Event-free survival (EFS) [days] was the shortest duration of the following: (a) Date of assessment indicating PD on the response page of the eCRF (Electronic Case Report Form) - date of randomisation + 1 day (b) Date of assessment indicating clinical progressive disease (PD) on the disease or responses pages of the of eCRF- date of randomisation + 1 day (c) Date of assessment indicating PD on the patient status page of the eCRF - date of randomisation +1 day (for patients who had not been censored before this time point) (d) Death date - date of randomisation +1 day Patients not being assessed PD, clinical PD, or death during the trial were censored. EFS was analysed with the Kaplan-Meier method for each of the treatment arms.

Phase II: Overall Survival

Overall survival [days] = (date of death - date of randomisation + 1 day), for patients with known date of death. Overall survival (censored) [days] = (date of last trial visit or follow-up - date of randomisation + 1 day), for patients who were still alive at time of database lock. Overall survival (OS) was analysed with the Kaplan-Meier method for each of the treatment arms.

Phase II: Relapse - Free Survival

Relapse-free survival [days] = (date of first recurrence of disease or death after entering the trial - date of first occurrence of CR or CRi after entering the trial+ 1 day) for patients with a recurrence (this value should be positive). Relapse-free survival (censored) [days] = (date of last trial visit or follow-up - date of first occurrence of CR or CRi after entering the trial + 1 day) for patients who did not experience recurrence of disease or death at the time of analysis.

Phase II: Remission Duration

Remission duration analysis was defined only for patients who achieved Complete remission (CR) or Complete remission with incomplete blood count recovery (CRi), and was measured from the date of attaining CR or CRi until the date of disease recurrence (relapse). For patients who died without report of relapse, remission duration was censored on the date of death, regardless of cause.

Phase II: Time to Remission

Time to remission [days] = (date of first occurrence of CR or CRi after entering the trial-date of randomisation + 1 day) for patients with an objective response.

Best Eastern Co-operative Oncology Group (ECOG) Performance Score From Baseline Until End of Treatment

ECOG performance score change from baseline to last visit of last cycle = ECOG performance score at last visit of the last cycle - ECOG performance score at baseline. ECOG performance score changes from baseline were also categorised on a 3-point categorical scale: deteriorated (-1), unchanged (0), and improved (1). The number of participants for category of ECOG score change is reported.

Total Clearance (CL) of Volasertib in Plasma After i.v (Intravenous) Administration of Volasertib

Total Clearance (CL) of Volasertib in Plasma after Intravenous (i.v.) Administration of Volasertib.

Apparent Volume of Distribution of Volasertib at Steady State (VSS)

Apparent Volume of Distribution of volasertib at steady state (VSS) following Intravenous (i.v.) administration.

Dose Normalized Maximum Measured Concentration of Cytarabine in Plasma (Cmax, Norm)

Cmax, norm: Maximum measured concentration of Cytarabine in plasma. The dose normalisation was done by dividing by the dose applied. Unit: nanogram/milliliter/milligram: ((ng/mL)/mg). Dose groups of Phase I were combined by dose normalizing as pre specified in the study protocol.

Dose Normalized Area Under the Concentration-Time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated up to 4 Hours

AUC0-4,norm: Area under the concentration-time curve of Cytarabine in plasma over the time interval from zero extrapolated to 4 hours. The dose normalisation was done by dividing by dose applied. Unit: nanogram*hour/milliliter/milligram: ((ng*h/mL)/mg). Dose groups of Phase I were combined by dose normalizing as pre specified in the study protocol.

Absolute QTcF (QT Interval Corrected for Heart Rate Using Fridericia's Formula) Intervals

ECG (Electro Cardio Gram) Measurements: Absolute QTcF (QT Interval (interval from the beginning of the QRS complex to the end of the T wave) Corrected for Heart Rate Using Fridericia's Formula) Intervals. The 350 mg + LDAC arm of phase I and II were combined into one arm to provide maximum information on QT changes and presented together with the Phase I schedule B 450 mg arm, as pre specified in the study protocol.

QTcF (QT Interval Corrected for Heart Rate Using Fridericia's Formula) Change From Baseline at Cycle 1

ECG Measurements: QTcF (QT Interval (interval from the beginning of the QRS complex to the end of the T wave) changes from baseline at each time point: The QTcF post baseline measurement obtained at time t minus baseline QTcF measurement. The 350 mg + LDAC arm of phase I and II were combined into one arm to provide maximum information on QT changes and presented together with the Phase I schedule B 450 mg arm, as pre specified in the study protocol.

Phase I Schedule A: Number of Participants With Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), Based on the Number of Patients With AEs With CTCAE Grade ≥3 During Cycle 1

Number of patients with AEs following in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported.

Phase I Schedule B: Number of Participants With Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), Based on the Number of Patients With AEs With CTCAE Grade ≥3 During Cycle 1

Number of patients with AEs following in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported.

Phase II: Number of Participants With Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), Based on the Number of Patients With AEs With CTCAE Grade ≥3 During All Cycles

Number of patients with AEs following in the in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported.

Full Information

NCT ID

NCT00804856

First Posted

September 18, 2008

Last Updated

December 2, 2022

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT00804856

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Completed

Study Start Date

November 27, 2008 (Actual)

Primary Completion Date

March 9, 2012 (Actual)

Study Completion Date

April 23, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia, Myeloid, Acute

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

180 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase I Schedule A. Volasertib 150 mg+LDAC

Arm Type

Experimental

Arm Description

Arm Title

Phase I Schedule A. Volasertib 200 mg+LDAC

Arm Type

Experimental

Arm Description

Arm Title

Phase I Schedule A. Volasertib 250 mg+LDAC

Arm Type

Experimental

Arm Description

Arm Title

Phase I Schedule A. Volasertib 300 mg+LDAC

Arm Type

Experimental

Arm Description

Arm Title

Phase I Schedule A. Volasertib 350 mg+LDAC

Arm Type

Experimental

Arm Description

Arm Title

Phase I Schedule A. Volasertib 400 mg+LDAC

Arm Type

Experimental

Arm Description

Arm Title

Phase I Schedule B. Volasertib 150 mg

Arm Type

Experimental

Arm Description

Volasertib 150 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

Arm Title

Phase I Schedule B. Volasertib 200 mg

Arm Type

Experimental

Arm Description

Volasertib 200 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

Arm Title

Phase I Schedule B. Volasertib 350 mg

Arm Type

Experimental

Arm Description

Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

Arm Title

Phase I Schedule B. Volasertib 400 mg

Arm Type

Experimental

Arm Description

Volasertib 400 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

Arm Title

Phase I Schedule B. Volasertib 450 mg

Arm Type

Experimental

Arm Description

Volasertib 450 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

Arm Title

Phase I Schedule B. Volasertib 500 mg

Arm Type

Experimental

Arm Description

Volasertib 500 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

Arm Title

Phase I Schedule B. Volasertib 550 mg

Arm Type

Experimental

Arm Description

Volasertib 550 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

Arm Title

Phase II Schedule C. LDAC

Arm Type

Active Comparator

Arm Description

Low-dose cytarabine (LDAC) monotherapy 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 days treatment cycle.

Arm Title

Phase II Schedule A. Volasertib 350 mg+LDAC

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Volasertib

Intervention Description

Volasertib administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

Intervention Type

Drug

Intervention Name(s)

Cytarabine

Intervention Description

Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

Primary Outcome Measure Information:

Title

Phase I: Maximum Tolerated Dose (MTD) of Volasertib in Combination With LDAC (Schedule A) and Volasertib Monotherapy (Schedule B)

Description

Time Frame

First Treatment cycle, up to 28 days.

Title

Phase II: Number of Patients With Objective Response (Complete Remission (CR) + Complete Remission With Incomplete Blood Count Recovery (CRi))

Description

Time Frame

The best overall response recorded during the time period from the start of the treatment until end of the treatment period, progression or death (whichever was earlier), up to 869 days.

Title

Phase I: Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)

Description

Time Frame

First Treatment cycle, up to 28 days.

Secondary Outcome Measure Information:

Title

Best Overall Response

Description

Time Frame

The best overall response recorded during the time period from the start of the treatment until end of the treatment period, progression or death (whichever was earlier), up to 869 days.

Title

Phase I: Number of Patients With Objective Response: Complete Remission or Complete Remission With Incomplete Blood Count Recovery (CR+CRi)

Description

Time Frame

The best overall response recorded during the time period from the start of the treatment until end of the treatment period, progression or death (whichever was earlier), up to 594 days.

Title

Phase II: Event Free Survival

Description

Time Frame

The patients that entered the trial, and measured from the date of randomization to the date of disease progression (treatment failure), relapse or death from any cause, whichever occurred first, up to 1000 days..

Title

Phase II: Overall Survival

Description

Time Frame

The patients that entered the trial, and measured from the date of randomisation until death from any cause, up to 1100 days..

Title

Phase II: Relapse - Free Survival

Description

Time Frame

The patients who achieved CR or CRi, and was measured from the date of attaining CR or CRi until the date of disease recurrence or death from any cause, whichever occurred first, up to 900 days.

Title

Phase II: Remission Duration

Description

Time Frame

The patients who achieved CR or CRi, and was measured from the date of attaining CR or CRi until the date of disease recurrence (relapse), up to 900 days.

Title

Phase II: Time to Remission

Description

Time to remission [days] = (date of first occurrence of CR or CRi after entering the trial-date of randomisation + 1 day) for patients with an objective response.

Time Frame

The patients who achieved CR or CRi, and was measured from the date of attaining CR or CRi until the date of disease recurrence (relapse), up to 158 days.

Title

Best Eastern Co-operative Oncology Group (ECOG) Performance Score From Baseline Until End of Treatment

Description

Time Frame

Baseline and End of Treatment (up to 869 days).

Title

Total Clearance (CL) of Volasertib in Plasma After i.v (Intravenous) Administration of Volasertib

Description

Total Clearance (CL) of Volasertib in Plasma after Intravenous (i.v.) Administration of Volasertib.

Time Frame

Cycle 1: -0:05 hour (h), 0:30h, 1:00h, 1:30h, 2h, 3h, 4h, 24h, 96h, 216h, 335:55h, 336:30h, 337h, 337:30h, 338h, 339h, 340h, 648h after first drug administration.

Title

Apparent Volume of Distribution of Volasertib at Steady State (VSS)

Description

Apparent Volume of Distribution of volasertib at steady state (VSS) following Intravenous (i.v.) administration.

Time Frame

Cycle 1: -0:05 hour (h), 0:30h, 1:00h, 1:30h, 2h, 3h, 4h, 24h, 96h, 216h, 335:55h, 336:30h, 337h, 337:30h, 338h, 339h, 340h, 648h after first drug administration.

Title

Dose Normalized Maximum Measured Concentration of Cytarabine in Plasma (Cmax, Norm)

Description

Time Frame

Cycle 1: -0:05 hour (h), 0:30h, 1:00h, 1:30h, 2h, 3h, 4h, 24h, 96h, 216h, 335:55h, 336:30h, 337h, 337:30h, 338h, 339h, 340h, 648h after first drug administration.

Title

Dose Normalized Area Under the Concentration-Time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated up to 4 Hours

Description

Time Frame

Cycle 1: -0:05 hour (h), 0:30h, 1:00h, 1:30h, 2h, 3h, 4h after first drug administration.

Title

Absolute QTcF (QT Interval Corrected for Heart Rate Using Fridericia's Formula) Intervals

Description

Time Frame

Baseline (Days -14 to -1) and day 1 (1 hour and 24 hours) after start of infusion.

Title

QTcF (QT Interval Corrected for Heart Rate Using Fridericia's Formula) Change From Baseline at Cycle 1

Description

Time Frame

Baseline (Days -14 to -1) and day 1 (1 hour and 24 hours) after start of infusion.

Title

Description

Number of patients with AEs following in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported.

Time Frame

First treatment cycle, up to 28 days.

Title

Description

Number of patients with AEs following in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported.

Time Frame

First treatment cycle, up to 28 days.

Title

Description

Number of patients with AEs following in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported.

Time Frame

From first drug administration until 21 days after the last trial drug administration in the last treatment cycle, up to 615 days.

Title

Description

Number of patients with AEs following in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported.

Time Frame

From first drug administration until 21 days after the last trial drug administration in the last treatment cycle, up to 597 days.

Title

Description

Number of patients with AEs following in the in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported.

Time Frame

From first drug administration until 21 days after the last trial drug administration in the last treatment cycle, up to 890 days.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Boehringer Ingelheim

Organizational Affiliation

Boehringer Ingelheim

Official's Role

Study Chair

Facility Information:

Facility Name

LKH-Univ. Hospital Graz

City

Graz

ZIP/Postal Code

8036

Country

Austria

Facility Name

AZ Sint-Jan Brugge

City

Brugge

ZIP/Postal Code

8000

Country

Belgium

Facility Name

Brussels - UNIV Saint-Luc

City

Bruxelles

ZIP/Postal Code

1200

Country

Belgium

Facility Name

UZ Leuven

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Princess Margaret Cancer Centre

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2M9

Country

Canada

Facility Name

Montreal General Hospital - McGill University Health Centre

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H3G 1A4

Country

Canada

Facility Name

CHUS Fleurimont

City

Sherbrooke

State/Province

Quebec

ZIP/Postal Code

J1H 5N4

Country

Canada

Facility Name

HOP Clémenceau, Hémato, Caen

City

Caen

ZIP/Postal Code

14033

Country

France

Facility Name

HOP, Centre Hospitalier René Dubos, Hémato, Paris

City

Cergy Pontoise Cedex

ZIP/Postal Code

95303

Country

France

Facility Name

HOP Dupuytren 1

City

Limoges

ZIP/Postal Code

87042

Country

France

Facility Name

HOP Edouard Herriot

City

Lyon Cedex 03

ZIP/Postal Code

69437

Country

France

Facility Name

CTR, fondation Paschetta, Hémato, Nice

City

Nice Cedex 2

ZIP/Postal Code

06189

Country

France

Facility Name

HOP Saint-Louis

City

Paris cedex 10

ZIP/Postal Code

75475

Country

France

Facility Name

CTR Henri Becquerel

City

Rouen Cedex

ZIP/Postal Code

76088

Country

France

Facility Name

Campus Virchow-Klinikum, Berlin

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

Universitätsklinikum Frankfurt

City

Frankfurt/Main

ZIP/Postal Code

60590

Country

Germany

Facility Name

Universitätsklinikum Freiburg

City

Freiburg

ZIP/Postal Code

79106

Country

Germany

Facility Name

Universitätsklinikum Hamburg-Eppendorf

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Facility Name

Universitätsklinikum Heidelberg

City

Heidelberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

Universitätsklinikum Schleswig-Holstein, Campus Kiel

City

Kiel

ZIP/Postal Code

24116

Country

Germany

Facility Name

Universitätsklinikum Münster

City

Münster

ZIP/Postal Code

48149

Country

Germany

Facility Name

Universitätsklinikum Ulm

City

Ulm

ZIP/Postal Code

89081

Country

Germany

Facility Name

A.O. Spedali Civili di Brescia

City

Brescia

ZIP/Postal Code

25123

Country

Italy

Facility Name

ASST Grande Ospedale Metropolitano Niguarda

City

Milano

ZIP/Postal Code

20162

Country

Italy

Facility Name

Azienda Ospedaliera Policlinico di Modena

City

Modena

ZIP/Postal Code

41100

Country

Italy

Facility Name

Haukeland Universitetssykehus

City

Bergen

ZIP/Postal Code

N-5021

Country

Norway

Facility Name

Oslo Universitetssykehus HF, Ullevål sykehus

City

Oslo

ZIP/Postal Code

N-0450

Country

Norway

12. IPD Sharing Statement

Citations:

PubMed Identifier

25006120

Citation

Dohner H, Lubbert M, Fiedler W, Fouillard L, Haaland A, Brandwein JM, Lepretre S, Reman O, Turlure P, Ottmann OG, Muller-Tidow C, Kramer A, Raffoux E, Dohner 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.

Results Reference

derived

Links:

URL

http://www.mystudywindow.com

Description

Related Info

Learn more about this trial

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

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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

Eligibility Criteria

Sites / Locations

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

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial