Phase I/IIa Trial to Investigate BI 6727 (Volasertib) as Monotherapy or in Combination With Cytarabine in Acute Myeloid Leukaemia
Condition: Leukemia, Myeloid, Acute
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Volasertib; Cytarabine
Intervention description: Volasertib administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).; Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.
Intervention MeSH terms: Cytarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 180.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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