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

University Hospital Muenster

Status and phase

Unknown

Phase 2

Phase 1

Conditions

Acute Myeloid Leukemia

Treatments

Drug: triple kinase inhibitor BIBF1120

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01488344

UKM10_0014

2011-001086-41 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment

140 estimated patients

Sex

All

Ages

60+ years old

Volunteers

No Healthy Volunteers

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