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

NCT ID: NCT00804856

Last Updated: 2023-10-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-27
• Study Completion Date: 2021-04-23

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.

Conditions

Leukemia, Myeloid, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I Schedule A. Volasertib 150 mg+LDAC

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.

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

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

Cytarabine

Intervention Type: DRUG

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

Phase I Schedule A. Volasertib 200 mg+LDAC

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.

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

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

Cytarabine

Intervention Type: DRUG

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

Phase I Schedule A. Volasertib 250 mg+LDAC

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.

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

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

Cytarabine

Intervention Type: DRUG

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

Phase I Schedule A. Volasertib 300 mg+LDAC

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.

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

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

Cytarabine

Intervention Type: DRUG

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

Phase I Schedule A. Volasertib 350 mg+LDAC

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.

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

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

Cytarabine

Intervention Type: DRUG

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

Phase I Schedule A. Volasertib 400 mg+LDAC

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.

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

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

Cytarabine

Intervention Type: DRUG

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

Phase I Schedule B. Volasertib 150 mg

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

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

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

Phase I Schedule B. Volasertib 200 mg

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

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

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

Phase I Schedule B. Volasertib 350 mg

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

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

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

Phase I Schedule B. Volasertib 400 mg

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

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

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

Phase I Schedule B. Volasertib 450 mg

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

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

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

Phase I Schedule B. Volasertib 500 mg

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

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

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

Phase I Schedule B. Volasertib 550 mg

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

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

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

Phase II Schedule C. LDAC

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

Group Type: ACTIVE_COMPARATOR

Cytarabine

Intervention Type: DRUG

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

Phase II Schedule A. Volasertib 350 mg+LDAC

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.

Group Type: EXPERIMENTAL

Volasertib

Intervention Type: DRUG

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

Cytarabine

Intervention Type: DRUG

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

Interventions

Volasertib

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

Intervention Type: DRUG

Cytarabine

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

LKH-Univ. Hospital Graz

Graz, , Austria

AZ Sint-Jan Brugge

Bruges, , Belgium

Brussels - UNIV Saint-Luc

Brussels, , Belgium

UZ Leuven

Leuven, , Belgium

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Montreal General Hospital - McGill University Health Centre

Montreal, Quebec, Canada

CHUS Fleurimont

Sherbrooke, Quebec, Canada

HOP Clémenceau, Hémato, Caen

Caen, , France

HOP, Centre Hospitalier René Dubos, Hémato, Paris

Cergy-Pontoise, , France

HOP Dupuytren 1

Limoges, , France

HOP Edouard Herriot

Lyon, , France

CTR, fondation Paschetta, Hémato, Nice

Nice, , France

HOP Saint-Louis

Paris, , France

CTR Henri Becquerel

Rouen, , France

Campus Virchow-Klinikum, Berlin

Berlin, , Germany

Universitätsklinikum Frankfurt

Frankfurt am Main, , Germany

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Universitätsklinikum Schleswig-Holstein, Campus Kiel

Kiel, , Germany

Universitätsklinikum Münster

Münster, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

A.O. Spedali Civili di Brescia

Brescia, , Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Azienda Ospedaliera Policlinico di Modena

Modena, , Italy

Haukeland Universitetssykehus

Bergen, , Norway

Oslo Universitetssykehus HF, Ullevål sykehus

Oslo, , Norway

Countries

Austria; Belgium; Canada; France; Germany; Italy; Norway

References

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.

Reference Type: DERIVED

PMID: 25006120 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.mystudywindow.com

Related Info

Other Identifiers

2008-003617-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1230.4

Identifier Type: -

Identifier Source: org_study_id