Phase I/II Trial: BIBF 1120 Added to Low-dose Cytarabine in Elderly Patients With Acute Myeloid Leukemia (AML)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
University Hospital Muenster
ClinicalTrials.gov Identifier:
NCT01488344
First received: November 15, 2011
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

RATIONALE: Low-dose cytarabine works in a minority of elderly patients with an acute myeloid leukemia unfit for intensive induction therapy by killing of leukemia cells. Addition of BIBF1120 to low-dose cytarabine might enhance the killing of leukemia cells.

PURPOSE: This phase I / II trial is studying how safe BIBF1120 can be combined with low-dose cytarabine (phase I) and how well the combination of low-dose cytarabine and BIBF1120 works in elderly patients with acute myeloid leukemia unfit for intensive chemotherapy (phase II).


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: triple kinase inhibitor BIBF1120
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single-arm, Open Label, Multi-center Phase I/II Trial to Assess the Safety and Efficacy of BIBF 1120 Added to Low-dose Cytarabine in Elderly Patients With AML Unfit for an Intensive Induction Therapy

Resource links provided by NLM:


Further study details as provided by University Hospital Muenster:

Primary Outcome Measures:
  • Phase I: defining maximum tolerated dose (MTD) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • Phase II: overall response rate (ORR) [ Time Frame: up to 6 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete remission (CR) rate [ Time Frame: up to 12 month ] [ Designated as safety issue: No ]
  • overall survival (OS) [ Time Frame: up to 12 month ] [ Designated as safety issue: No ]
  • relapse-free survival (RFS)of the responding patients [ Time Frame: up to 12 month ] [ Designated as safety issue: No ]
  • number of participants with adverse events as a measure of safety and tolerability [ Time Frame: up to 12 month ] [ Designated as safety issue: No ]
  • ORR rate of the Flt3-mutated patients versus the Flt3-wildtype patients [ Time Frame: up to 12 month ] [ Designated as safety issue: No ]
  • CR rate of the Flt3-mutated patients versus the Flt3-wildtype patients [ Time Frame: up to 12 month ] [ Designated as safety issue: No ]
  • OS of the Flt3-mutated patients versus the Flt3-wildtype patients [ Time Frame: up to 12 month ] [ Designated as safety issue: No ]
  • time to response (CR, CRp, CRi) of the responding patients [ Time Frame: up to 12 month ] [ Designated as safety issue: No ]
    CRp = complete remission with incomplete platelet recovery CRi = complete remission with incomplete neutrophil recovery


Estimated Enrollment: 140
Study Start Date: March 2012
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBF 1120 Drug: triple kinase inhibitor BIBF1120
triple kinase inhibitor BIBF1120 is given in addition to low-dose cytarabine

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with newly diagnosed AML (except APL) according to the FAB or WHO classification, including AML evolving from MDS or other hematological diseases and AML after previous cytotoxic therapy or radiation (secondary AML), with medical contraindications against or not willing to receive a standard induction and consolidation therapy.
  • Bone marrow aspirate or biopsy must contain > 20% blasts of all nucleated cells. In AML FAB M6 ≥ 30% of non-erythroid cells in the bone marrow must be leukemic blasts. In patients with 20-30% blasts, the indication for a treatment with hypomethylating agents (5-azacitidine or decitabine) should be considered prior to inclusion into the trial.
  • Age ≥ 60 years
  • Informed consent, personally signed and dated to participate in the study
  • Male patients enrolled in this trial must use adequate barrier birth control measures during the course of treatment and for at least 3 months after the last administration of study therapy (low-dose cytarabine and/or BIBF 1120).

Exclusion Criteria:

  • Patients with 20-30% bone marrow blasts which are qualifying for and consenting into a therapy with hypomethylating agents
  • Patients who are eligible for and consenting into a standard chemotherapy
  • Known central nervous system manifestation of AML
  • Inadequate liver function (ALT and AST ≥ 2.5 x ULN) if not caused by leukemic infiltration
  • Known chronically active hepatitis C infection or acute hepatitis
  • Chronically impaired renal function (creatinin clearance < 30 ml/min)
  • Uncontrolled hypertension with a resting pressure systolic > 160 mmHg or diastolic > 95 mmHg despite adequate treatment
  • severe trauma or surgery within 4 weeks of study entry
  • severe, non-healing wounds, ulcer or fracture
  • Uncontrolled active infection
  • Concurrent malignancies other than AML or other severe diseases which in the opinion of the investigator are likely to influence the endpoint assessment
  • Hypersensitivity to cytarabine (not including drug fever or exanthema)
  • Previous treatment of AML except hydroxyurea up to 24 hours before study medication
  • Previous therapy with tyrosine kinase inhibitors or angiogenesis inhibitors
  • Parallel participation in another clinical trial for the same indication. Eligibility of patients with investigational drug therapy outside of this trial during or within 4 weeks of study entry should be discussed with the study office prior to study entry
  • Any severe concomitant condition, which makes it undesirable for the patient to participate in the study or which could jeopardize compliance 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: NCT01488344

Locations
Germany
Universitätsklinikum Münster, Medizinische Klinik und Poliklinik A
Münster, Germany, 48149
Sponsors and Collaborators
University Hospital Muenster
Boehringer Ingelheim
Investigators
Principal Investigator: Utz Krug, MD University Hospital Münster, Medizinische Klinik und Poliklinik A
  More Information

No publications provided

Responsible Party: University Hospital Muenster
ClinicalTrials.gov Identifier: NCT01488344     History of Changes
Other Study ID Numbers: UKM10_0014, 2011-001086-41
Study First Received: November 15, 2011
Last Updated: December 10, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Nintedanib
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
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014