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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01488344
• Other study ID #: UKM10_0014
• Secondary ID: 2011-001086-41
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: November 15, 2011
• Last updated: December 10, 2013
• Start date: March 2012

Study information

• Verified date: December 2013
• Source: University Hospital Muenster
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 140
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• triple kinase inhibitor BIBF1120
triple kinase inhibitor BIBF1120 is given in addition to low-dose cytarabine

Locations

Country	Name	City	State
Germany	Universitätsklinikum Münster, Medizinische Klinik und Poliklinik A	Münster

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Muenster	Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I: defining maximum tolerated dose (MTD)		4 weeks	Yes
Primary	Phase II: overall response rate (ORR)		up to 6 month	No
Secondary	Complete remission (CR) rate		up to 12 month	No
Secondary	overall survival (OS)		up to 12 month	No
Secondary	relapse-free survival (RFS)of the responding patients		up to 12 month	No
Secondary	number of participants with adverse events as a measure of safety and tolerability		up to 12 month	No
Secondary	ORR rate of the Flt3-mutated patients versus the Flt3-wildtype patients		up to 12 month	No
Secondary	CR rate of the Flt3-mutated patients versus the Flt3-wildtype patients		up to 12 month	No
Secondary	OS of the Flt3-mutated patients versus the Flt3-wildtype patients		up to 12 month	No
Secondary	time to response (CR, CRp, CRi) of the responding patients	CRp = complete remission with incomplete platelet recovery CRi = complete remission with incomplete neutrophil recovery	up to 12 month	No