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

Condition(s) targeted: Leukemia, Myeloid, Acute

Intervention: BI 811285 (d 1 and 15) (Drug); BI 811283 (d1) (Drug); Cytarabine (Drug); Cytarabine (Drug); Cytarabine (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Boehringer Ingelheim Pharmaceuticals

Official(s) and/or principal investigator(s):
Boehringer Ingelheim, Study Chair, Affiliation: Boehringer Ingelheim Pharmaceuticals

Overall contact:
Boehringer Ingelheim Call Center, Phone: 1-800-243-0127, Email: clintriage.rdg@boehringer-ingelheim.com

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, two schedules of BI 811283 in combination with LD-Ara-C will be investigated. In the phase I part, the dose of BI 811283 will be escalated to determine the maximum tolerated dose (MTD) of the two dosing schedules of BI 811283 in combination with LD-Ara-C.

In the phase IIa part, the two combination schedules of BI 811283 at MTD with LD-Ara-C and one LD-Ara-C monotherapy schedule will be investigated to determine the efficacy of the two combination schedules in comparison to LD-Ara-C monotherapy in previously untreated AML patients ineligible for intensive treatment.

Official title: An Open Phase I/IIa Trial to Investigate the Maximum Tolerated Dose, Safety, Efficacy and Pharmacokinetics of BI 811283 in Combination With Cytarabine in Patients With Previously Untreated Acute Myeloid Leukaemia Ineligible for Intensive Treatment

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Phase I part: maximum tolerated dose (MTD) of two schedules of BI 811283 in combination with low-dose cytarabine (LD-Ara-C).

Phase IIa part: Response (complete remission, CR; complete remission with incomplete blood count recovery, CRi)

Secondary outcome:

Pharmacokinetics of BI 811283 BS in the presence of cytarabine

Incidence and intensity of adverse events graded according to CTCAE (version 3.0)

Incidence of dose limiting toxicity.

Partial remission.

Event free survival.

Relapse free survival.

Remission duration.

Overall Survival.

Supportive care requirements (blood products, antibiotic usage, hospitalisation).

Pharmacodynamic monitoring: drug effect on leukaemia cells (e.g. polyploidy, histone H3 phosphorylation, morphologic changes).

Pharmacokinetics of cytarabine after a single dose and at steady state when given alone and in combination with BI 811283 BS (free base of BI 811283)

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Boehringer Ingelheim Call Center, Phone: 1-800-243-0127, Email: clintriage.rdg@boehringer-ingelheim.com

1247.3.49007 Boehringer Ingelheim Investigational Site, Berlin, Germany; Recruiting

1247.3.49008 Boehringer Ingelheim Investigational Site, Bonn, Germany; Recruiting

1247.3.49005 Boehringer Ingelheim Investigational Site, Frankfurt/Main, Germany; Recruiting

1247.3.49004 Boehringer Ingelheim Investigational Site, Freiburg, Germany; Recruiting

1247.3.49006 Boehringer Ingelheim Investigational Site, Hamburg, Germany; Recruiting

1247.3.49003 Boehringer Ingelheim Investigational Site, Heidelberg, Germany; Recruiting

1247.3.49002 Boehringer Ingelheim Investigational Site, Münster, Germany; Recruiting

1247.3.49001 Boehringer Ingelheim Investigational Site, Ulm, Germany; Recruiting

Starting date: May 2008
Last updated: September 14, 2010