patients with acute myeloid leukaemia (AML) that are not eligible for intensive treatment MedDRA version: 20.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: Volasertib
Product Code: BI 6727
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Volasertib
Current Sponsor code: BI 6727
Concentration unit: mg/ml milligram(s)/millilit
Sponsors
Boehringer Ingelheim Pharma GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion 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 (except hydroxyurea) 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 =65 years) yes F.1.3.1 Number of subjects for this age range 110
Exclusion criteria
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) •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 µmol/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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Phase I part: MTD of BI 6727 monotherapy and BI 6727 in combination with LD-Ara-C Phase IIa part: Efficacy (complete remission, CR; complete remission with incomplete blood count recovery, CRi) ;Timepoint(s) of evaluation of this end point: MTD: at the end of phase I part Efficacy: will be analyzed and reported after all patients have either stopped treatment or received at least four treatment cycles. ;Main Objective: The trial will be performed in two parts, a phase I part and a phase IIa part. In the phase I part, BI 6727 will be investigated as monotherapy and in combination with low dose cytarabine (LD-Ara-C) in patients with relapsed/refractory AML ineligible 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. A safety analysis and conclusion on the MTD will be performed after the MTD is determined in treatment schedule A. The selection of the recommended dose for the phase II part will be based on the MTD and the safety observed during treatment beyond the 1st cycle. In the phase IIa part, the combination of BI 6727 (at the recommended dose for phase II) with LD-Ara-C and LD-Ara-C monotherapy will be investigated to explore the efficacy of the combination in comparison to LD-Ara-C monotherapy in previously untreated AML patients ineligible for intensive treatment.;Secondary Objective: Further analysis of safety parameters including: Incidence and intensity of adverse events graded according to CTCAE (version 3.0), Incidence of dose limiting toxicity, QTc changes during and after intravenous infusion of BI 6727. Pharmakokinetic analysis inluding: Pharmacokinetics of BI 6727 when given alone and in combination with cytarabine, Pharmacokinetics of cytarabine after a single dose when given alone and in combination with BI 6727, Pharacodynamic analysis: drug effect on leukaemia cells Furhter analysis of efficacy parame | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.) Incidence and intensity of adverse events graded according to CTCAE (version 3.0) 2.) Incidence of dose limiting toxicity (DLT) 3.) Pharmacokinetics of BI 6727 when given alone and in combination with cytarabine 4.) Pharmacokinetics of cytarabine after a single dose when given alone and in combination with BI 6727 5.) Pharmacodynamic monitoring: drug effect on leukaemia cells 6.) Partial remission (PR) 7.) Event free survival (EFS) 8.) Relapse free survival 9.) Remission duration 10.) Overall survival (OS) 11.) QTc changes during and after intravenous infusion of BI 6727 12.) Supportive care requirements (blood products, antibiotic usage, hospitalisation) ;Timepoint(s) of evaluation of this end point: when the last patient has completed his / her last visit. | — |
Countries
Austria, Belgium, Canada, France, Germany, Italy, Norway
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed