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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00632749
First received: March 4, 2008
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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


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:


Further study details as provided by Boehringer Ingelheim:

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 ]

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 ]
  • 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 ]
  • Response (complete remission, CR; complete remission with incomplete blood count recovery, CRi) [ Time Frame: Time Frame: minimum 4 weeks, maximum n/a ] [ Designated as safety issue: No ]

Enrollment: 68
Study Start Date: May 2008
Study Completion Date: March 2014
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00632749     History of Changes
Other Study ID Numbers: 1247.3, 2007-005684-10
Study First Received: March 4, 2008
Last Updated: April 30, 2014
Health Authority: Germany: Bundesinstitut fuer Arzneimittel und Medizinprodukte

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia
Leukemia, Myeloid, Acute
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 September 22, 2014