A study of volasertib in combination with low-dose cytarabine in patientsaged 65 years and above with previously untreated acute myeloid leukaemia, who are ineligible for intensive remission induction therapy

Phase 1

Conditions: previously untreated acute myeloid leukaemia in patients >= 65 years and ineligible for intensive remission induction therapy
MedDRA version: 21.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-002487-27-IT

Lead Sponsor: BOEHRINGER ING.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 770

Inclusion Criteria

1. Age >= 65years. 2. Cytologically/histologically confirmed AML according to WHO classification; (except for acute promyelocytic leukaemia (APL)). 3. Previously untreated AML (except for hydroxyurea and/or corticosteroid therapy for no more than 28 days (cumulative)). Previous therapy for MDS is allowed. 4. Investigator considers patient ineligible for intensive remission induction therapy based on documented medical reasons (e.g. disease characteristics like AML genetics, type of AML (de novo or secondary), and patient characteristics like performance score, concomitant diagnoses, organ dysfunctions). 5. Patient is eligible for LDAC treatment. 6. Eastern Cooperative Oncology Group (ECOG) performance score <= 2 at screening. 7. Signed and dated written informed consent by start date of Screening visit in accordance with GCP and local legislation.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 770

Exclusion Criteria

1. Prior or concomitant chemotherapy for AML (with the exception of hydroxyurea and/or corticosteroid therapy for no more than 28 days (cumulative)). Please note that any prior therapy for MDS is allowed. 2. Treatment with any investigational drug within 2 weeks before first administration of present trial drug. 3. Acute promyelocytic leukaemia (French-American-British (FAB) classification subtype M3). 4. Current clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukaemic CNS involvement (no lumbar puncture required, clinical assessment per investigator's judgement is sufficient). 5. Hypersensitivity to one of the trial drugs or the excipients. 6. Severe illness or organ dysfunction involving the heart, kidney, liver or other organ system (e.g. active infection, clinically relevant impairment of cardiac function, severe heart failure/cardiac insufficiency, unstable angina pectoris or history of recent myocardial infarction), which in the opinion of the investigator precludes treatment with LDAC. 7. QTcF prolongation > 470 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome).The QTcF will be calculated as the mean of the 3 ECGs taken at screening. 8. Total bilirubin > 3 x ULN. 9. Creatinine clearance (CLcr) < 30 ml/min (estimated creatinine clearance by the Cockcroft-Gault (C-G) equation (see Appendix 10.2 for the formula). 10. Active hepatitis B or hepatitis C, or laboratory evidence for a chronic infection. 11. HIV infection. 12. Second malignancy currently requiring active therapy (except for hormonal/antihormonal treatment, e.g. in prostate or breast cancer). 13. Any significant concurrent psychiatric disorder or social situation that according to the investigator's judgement would compromise patient's safety or compliance, interfere with consent, study participation, or interpretation of study results. 14. Known or suspected active alcohol or drug abuse. 15. Patient unable to comply with the protocol, in the opinion of the investigator. 16. 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 and for a minimum of 6 months after study treatment.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the efficacy, of intravenous volasertib + subcutaneous low-dose cytarabine in patients >= 65 years of age with previously untreated acute myeloid leukaemia, ineligible for intensive remission induction therapy. Efficacy will be determined primarily based on remission rate (CR+CRi) and overall survival (OS).;Secondary Objective: To investigate the safety, and pharmacokinetics of intravenous volasertib + subcutaneous low-dose cytarabine in patients >= 65 years of age with previously untreated acute myeloid leukaemia, ineligible for intensive remission induction therapy.;Primary end point(s): Complete Remission (CR) and Complete Remission with incomplete blood count recovery (CRi), based on blinded central review.;Timepoint(s) of evaluation of this end point: Response assessment is done at the end of every 2nd cycle during treatment period. In case of suspected disease progression a bone marrow examination should be performed as soon as possible.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Key secondary endpoint: Overall Survival (OS). Secondary endpoints: Event-Free Survival (EFS), Relapse-Free Survival (RFS), safety (AE), pharmacokinetics (PK);Timepoint(s) of evaluation of this end point: OS: all randomised patients are followed until death, lost to follow-up or withdrawal of consent. EFS: defined for all randomised patients, and measured from date of randomisation to date of progression or relapse, or death, whichever occurs first. RFS: defined only for patients achieving CR or CRi; measured from date of remission until date of relapse or death. Relapse or progression are evaluated at each response assessment. After end of active treatment follow-up visits will occur every 12 weeks. All adverse events occurring during the trial will be collected. Blood for PK will be collected at specified time points during C1 and C2 (optional at C4 and C6).

Related Trials