Relapsed or refractory acute myeloid leukemia in adult patients who are considered not to benefit from / not to be eligible for intensive salvage therapy and/or stem cell transplantation and have no established treatment options MedDRA version: 13.1 Level: LLT Classification code 10066638 Term: Acute myeloid leukemia progression System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 13.1 Level: LLT Classification code 10000886 Term: A
Conditions
Sponsors
Boehringer Ingelheim AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male or female adult with relapsed or refractory AML (except for acute promyelocytic leukemia, APL), considered not to benefit from / not to be eligible for standard intensive salvage therapy and / or stem cell transplantation based one of the following criteria: a. AML patient = 60 years who fails to achieve complete remission after standard anthracycline-based induction or at least 2 cycles of non-anthracycline based induction b. Relapsed AML patient = 60 years and at least one of the following: •CR1 (first complete remission) 1st relapse c. AML patient =65 years) yes F.1.3.1 Number of subjects for this age range 400
Exclusion criteria
Exclusion criteria: 1) Previously untreated AML 2) Patient with Acute Promyelocytic Leukemia [AML subtype M3 according to the French-American-British (FAB) classification] 3) Hypersensitivity to one of the trial drugs or the excipients 4) Second malignancy currently requiring active therapy. However, patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated, or a radical prostatectomy or definitive radiotherapy has been performed. 5) Current clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukemic CNS involvement (no lumbar puncture required, clinical assessment per investigator’s judgement is sufficient) 6) QTcF prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome, QTcF > 470 ms, etc.). 7) Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 2.5 x the upper limit of normal (ULN), or AST or ALT > 5 x the ULN in case of known leukemia liver involvement 8) Prothrombin time (PT) > 1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin) 9) Total Bilirubin > 1.5 mg/dL (> 26 µmol/L, SI unit equivalent) (unless elevation is thought to be due to hepatic infiltration by AML, Gilbert syndrome, or hemolysis) 10) Serum creatinine > 2 mg/dL 11) 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 would interfere with the evaluation of the safety of the test drug or limit compliance with trial requirements 12) 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 13) Concomitant anti-leukemic treatment 14) Concomitant anti-infective therapy which, in the opinion of the investigator, is considered relevant for the evaluation of the efficacy or safety of the trial drug 15) Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate treatment) 16) Contraindications for cytarabine treatment according to the manufacturer’s product information provided in the ISF (applicable to patients randomized to Arm A) 17) Contraindications for the specific cytotoxic anti-leukemic product selected by the investigator according to the manufacturer’s product information (applicable to patients randomized to Arm B) 18) Female patients of childbearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial and for a minimum of 6 months after study treatment 19) Pregnant or breast feeding patients 20) Treatment with any investigational drug within 2 weeks of administration of first study medication dose or within less than five half times of the investigational drug before treatment with the present trial drug and / or persistence of toxicities of prior anti-leukemic therapies which are deemed clinically relevant 2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To test whether patients with relapsed or refractory acute myeloid leukemia with no established therapeutic options treated with combination of volasertib (BI 6727) plus low-dose cytarabine will derive greater benefit over patients treated with investigator's choice of the best alternative antileukemic therapy;Secondary Objective: Additional information on safety, health-related quality of life, pharmacogenetics, and pharmacokinetics will be collected;Primary end point(s): The Primary endpoints for efficacy are Complete Remission (CR) for the phase II portion of the trial and Overall Survival (OS) for the phase III portion of the trial;Timepoint(s) of evaluation of this end point: CR: assessment of response is done at the end of each treatment cycle. One interim analysis will be performed when approximately 300 patients are treated and evaluable for response. This cutoff defines the end of the Phase II portion of the trial. OS: Patient's vital status is collected at each follow-up visit (at 12-week intervals ).The Phase III data for this trial will be analyzed with a cutoff date for safety and efficacy data collection after all ongoing patients have discontinued treatment/dropped out or received at least four cycles of treatment. Overall mortality rates during the first 4 and 8 weeks after the initial dose of study medication will also be tabulated for each treatment group. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints for efficacy are the following: 1) Event free survival (EFS) 2) Complete Remission with incomplete blood count recovery (CRi) 3) Relapse Free Survival (RFS) 4) Remission duration ;Timepoint(s) of evaluation of this end point: Assessment of response (remission, relapse, progression) is done at the end of each treatment cycle (which will vary according to the treatment cycle duration for the different study drugs). Event free survival (EFS), Relapse Free Survival (RFS), and Remission duration will be analyzed after database lock. | — |
Countries
Austria, Belgium, Czech Republic, Finland, France, Germany, India, Italy, Korea, Republic of, Netherlands, Poland, Spain, Sweden, Taiwan, United States
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed