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

Boehringer Ingelheim

Status and phase: Completed; Phase 2

Conditions: Leukemia, Myeloid, Acute

Treatments: Drug: Volasertib; Drug: Cytarabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00804856

1230.4

2008-003617-27 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 180 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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180 participants in 15 patient groups

Phase I Schedule A. Volasertib 150 mg+LDAC

Experimental group

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.

Treatment:

Drug: Volasertib

Drug: Cytarabine

Phase I Schedule A. Volasertib 200 mg+LDAC

Experimental group

Description:

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.

Treatment:

Drug: Volasertib

Drug: Cytarabine

Phase I Schedule A. Volasertib 250 mg+LDAC

Experimental group

Description:

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.

Treatment:

Drug: Volasertib

Drug: Cytarabine

Phase I Schedule A. Volasertib 300 mg+LDAC

Experimental group

Description:

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.

Treatment:

Drug: Volasertib

Drug: Cytarabine

Phase I Schedule A. Volasertib 350 mg+LDAC

Experimental group

Description:

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.

Treatment:

Drug: Volasertib

Drug: Cytarabine

Phase I Schedule A. Volasertib 400 mg+LDAC

Experimental group

Description:

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.

Treatment:

Drug: Volasertib

Drug: Cytarabine

Phase I Schedule B. Volasertib 150 mg

Experimental group

Description:

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

Treatment:

Drug: Volasertib

Phase I Schedule B. Volasertib 200 mg

Experimental group

Description:

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

Treatment:

Drug: Volasertib

Phase I Schedule B. Volasertib 350 mg

Experimental group

Description:

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

Treatment:

Drug: Volasertib

Phase I Schedule B. Volasertib 400 mg

Experimental group

Description:

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

Treatment:

Drug: Volasertib

Phase I Schedule B. Volasertib 450 mg

Experimental group

Description:

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

Treatment:

Drug: Volasertib

Phase I Schedule B. Volasertib 500 mg

Experimental group

Description:

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

Treatment:

Drug: Volasertib

Phase I Schedule B. Volasertib 550 mg

Experimental group

Description:

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

Treatment:

Drug: Volasertib

Phase II Schedule C. LDAC

Active Comparator group

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.

Treatment:

Drug: Cytarabine

Phase II Schedule A. Volasertib 350 mg+LDAC

Experimental group

Description:

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.

Treatment:

Drug: Volasertib

Drug: Cytarabine