BI 811283 in Combination With Cytarabine in Previously Untreated AML Ineligible for Intensive Treatment

Boehringer Ingelheim68 enrolled

Overview

Investigation of maximum tolerated dose, safety, efficacy and pharmcokinetics of BI 811283 in combination with cytarabine (LD-Ara-C) in previously untreated acute myeloid leukaemia (AML) patients

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Leukemia, Myeloid, Acute

Interventions

BI 811283 (d 1 and 15)DRUG

BI 811283 (24 hours i.v.c.i.) on day 1 and 15 of a 4-week treatment cycle

CytarabineDRUG

Cytarabine 2 x 20 mg/d s.c. on days 1-10 of a 4-week treatment cycle

BI 811283 (d1)DRUG

BI 811283 (24 hours i.v.c.i.) on day 1 of a 4-week treatment cycle

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: * Male or female adult with previously untreated acute myeloid leukaemia (AML) * Confirmed diagnosis of AML according to the WHO definition (except for acute promyelocytic leukaemia, APL) * Patient is considered ineligible for intensive treatment * Patient is eligible for low-dose cytarabine (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: * Patient with APL (AML subtype M3 according to the French-American-British (FAB) classification). * Relapsed or treatment refractory AML. * Hypersensitivity to one of the trial drugs or the excipients. * Other malignancy requiring treatment. * Known central nervous system involvement. * Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (ULN). * INR \> 1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin). * Bilirubin greater than 1.5 mg/dl. * Serum creatinine greater than 2.0 mg/dl. * LVEF (Left ventricular ejection fraction) \< 50% in echocardiography or clinical congestive heart failure New York Heart Association (NYHA) grade III or IV. * Concomitant intercurrent illness, which would compromise the evaluation of efficacy or safety of the trial drug, e.g. active severe infection, unstable angina pectoris or cardiac arrhythmia. * 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 (i.e. other chemo- or immunotherapy, see also section 4.2.2). * Contraindications for cytarabine treatment according to the summary of product characteristics (SPC). * Patients who are sexually active and unwilling to use a medically acceptable method of contraception during the trial (hormonal contraception, intrauterine device, condom with spermicide, etc.). * Pregnant or nursing female patients. * Patient unable to comply with the protocol.

Locations (7)

1247.3.49007 Boehringer Ingelheim Investigational Site

Berlin, Germany

1247.3.49005 Boehringer Ingelheim Investigational Site

Frankfurt am Main, Germany

1247.3.49004 Boehringer Ingelheim Investigational Site

Freiburg im Breisgau, Germany

1247.3.49006 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Outcomes

Primary Outcomes

The Maximum Tolerated Dose (MTD) of 2 Schedules of BI 811283 in Combination With Cytarabine.

The MTD was defined as the highest dose at which 6 patients were treated and less than 2 patients who experienced a dose limiting toxicities (DLT) within the first cycle of treatment.The MTD was defined based on safety data from the first cycle only. It was determined using a standard "3 + 3 design with de-escalation".

Time frame: up to 28 days of treatment

Secondary Outcomes

Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi])

Response to treatment was evaluated according to the following criteria (modified from the National Cancer Institute/Cancer and Leukemia Group B criteria: The best overall response was defined as the best overall response recorded during the time period from the start of the treatment until the end of the treatment period, progression or death (whichever was earlier). Possible categories for best overall response were CR, CRi, Partial remission (PR), no change (NC), Progressive disease (PD) and no assessment. * Complete remission (CR): morphologically leukaemia free state (i.e. bone marrow with \< 5% blasts by morphologic criteria and no Auer rods, no evidence of extramedullary leukaemia) and absolute neutrophil count ≥ 1,000/μL and platelets \> 100,000/μL. * Complete remission with incomplete blood count recovery ("incomplete" CR, CRi).All of the above criteria for CR had to be met, except that neutrophils \< 1,000/μL or platelets \< 100,000/μL in the blood.

Time frame: Data collected up to cut-off date 20Oct2011, Up to 1239 days

Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0)

The severity and timing of AEs indicates how well the treatment regimen was tolerated. Toxicities were evaluated using the common terminology criteria for adverse events (CTCAE) grading scheme.

Time frame: Data from first treatment administration until cut-off date of 20 October 2011; up to 1239 days

Incidence of Dose Limiting Toxicity (DLT)

Data from ClinicalTrials.gov

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Cytarabine 2 x 20 mg/d s.c. on days 1-10 of a 4-week treatment cycle

1247.3.49003 Boehringer Ingelheim Investigational Site

Heidelberg, Germany

1247.3.49002 Boehringer Ingelheim Investigational Site

Münster, Germany

1247.3.49001 Boehringer Ingelheim Investigational Site

Ulm, Germany

Number of participants with DLT in the first cycle (28 days) for the determination of the maximum tolerated dose (MTD)

Time frame: up to 28 days of treatment

Partial Remission

Response to treatment was evaluated according to the following criteria (modified from the National Cancer Institute/Cancer and Leukemia Group B criteria; The best overall response was defined as the best overall response recorded during the time period from the start of the treatment until the end of the treatment period, progression or death (whichever was earlier). Possible categories for best overall response were CR, CRi, Partial remission (PR), no change (NC), Progressive disease (PD) and no assessment. Partial remission (PR). All of the criteria for CR had to be met, except that the bone marrow had to contain ≥ 5% but less than 25% blasts (or ≤ 50% of initial blast count), or \< 5% blasts in the presence of Auer rods or abnormal morphology.

Time frame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days

Event Free Survival (EFS)

EFS was defined as the duration of time from randomisation to time of treatment failure (i.e. PD), relapse from CR, or death from any cause, whichever came first.

Time frame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days

Relapse Free Survival

Relapse-free survival was defined only for patients who achieved CR/CRi and was measured from the date of attaining CR/CRi until the date of recurrence or death from any cause, whichever occurred first. Number of patients having relapse free survival are presented.

Time frame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days

Remission Duration

Remission duration analysis was defined only for patients who achieved CR, and was measured from the date of attaining CR until the date of disease recurrence (relapse). For patients who died without report of relapse, remission duration was censored on the date of death, regardless of the cause.

Time frame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days

Overall Survival (OS)

OS was defined for all patients that entered the trial, and measured from the date of randomization until death from any cause.

Time frame: Data collected up to cut-off date 20 Oct 2011, Up to 1239 days

Cmax (Maximum Measured Concentration of BI 811283 in Plasma)

Cmax (maximum measured concentration of BI 811283 in plasma) during Cycle 1