BI 811283 in Combination With Cytarabine in Previously Untreated AML Ineligible for Intensive Treatment - Full Text View

Purpose

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.

Condition	Intervention	Phase
Leukemia, Myeloid, Acute	Drug: BI 811285 (d 1 and 15) Drug: Cytarabine Drug: BI 811283 (d1)	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: 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

Resource links provided by NLM:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Leukemia

Drug Information available for: Cytarabine

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:

Phase I part: maximum tolerated dose (MTD) of two schedules of BI 811283 in combination with low-dose cytarabine (LD-Ara-C). [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Phase IIa part: Response (complete remission, CR; complete remission with incomplete blood count recovery, CRi) [ Time Frame: minimum 4 weeks, maximum n/a ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pharmacokinetics of BI 811283 BS in the presence of cytarabine [ Time Frame: during the first 4-week treatment cycle ] [ Designated as safety issue: No ]
Incidence and intensity of adverse events graded according to CTCAE (version 3.0) [ Time Frame: minimum 4 weeks, maximum n/a ] [ Designated as safety issue: No ]
Incidence of dose limiting toxicity. [ Time Frame: minimum 4 weeks, maximum n/a ] [ Designated as safety issue: No ]
Partial remission. [ Time Frame: minimum 4 weeks, maximum n/a ] [ Designated as safety issue: No ]
Event free survival. [ Time Frame: minimum 4 weeks, maximum n/a ] [ Designated as safety issue: No ]
Relapse free survival. [ Time Frame: minimum 4 weeks, maximum n/a ] [ Designated as safety issue: No ]
Remission duration. [ Time Frame: minimum 4 weeks, maximum n/a ] [ Designated as safety issue: No ]
Overall Survival. [ Time Frame: minimum 4 weeks, maximum n/a ] [ Designated as safety issue: No ]
Supportive care requirements (blood products, antibiotic usage, hospitalisation). [ Time Frame: minimum 4 weeks, maximum n/a ] [ Designated as safety issue: No ]
Pharmacodynamic monitoring: drug effect on leukaemia cells (e.g. polyploidy, histone H3 phosphorylation, morphologic changes). [ Time Frame: during the first 4-week treatment cycle ] [ Designated as safety issue: No ]
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) [ Time Frame: during the first 4-week treatment cycle ] [ Designated as safety issue: No ]

Enrollment:	68
Study Start Date:	May 2008
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Schedule A BI 811283 on days 1 and 15 in combination with LD-Ara-C	Drug: BI 811285 (d 1 and 15) BI 811283 (24 hours i.v.c.i.) on day 1 and 15 of a 4-week treatment cycle Drug: Cytarabine Cytarabine 2 x 20 mg/d s.c. on days 1-10 of a 4-week treatment cycle
Experimental: Schedule B BI 811283 on day 1 only in combination with LD-Ara-C	Drug: Cytarabine Cytarabine 2 x 20 mg/d s.c. on days 1-10 of a 4-week treatment cycle Drug: BI 811283 (d1) BI 811283 (24 hours i.v.c.i.) on day 1 of a 4-week treatment cycle
Active Comparator: Schedule C Control arm in phase IIa: LD-Ara-C (2x20 mg/d on days 1-10)	Drug: Cytarabine Cytarabine 2 x 20 mg/d s.c. on days 1-10 of a 4-week treatment cycle

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00632749

Locations

Germany
1247.3.49007 Boehringer Ingelheim Investigational Site
Berlin, Germany
1247.3.49005 Boehringer Ingelheim Investigational Site
Frankfurt/Main, Germany
1247.3.49004 Boehringer Ingelheim Investigational Site
Freiburg, Germany
1247.3.49006 Boehringer Ingelheim Investigational Site
Hamburg, Germany
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

Sponsors and Collaborators

Boehringer Ingelheim Pharmaceuticals

Investigators

Study Chair:

Boehringer Ingelheim

Boehringer Ingelheim Pharmaceuticals

More Information

No publications provided

Responsible Party:	Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00632749 History of Changes
Other Study ID Numbers:	1247.3, 2007-005684-10
Study First Received:	March 4, 2008
Last Updated:	August 22, 2012
Health Authority:	Germany: Bundesinstitut fuer Arzneimittel und Medizinprodukte

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 21, 2013