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

NCT01488344 | Unknown Phase 1 DMC

• 2 other identifiers: UKM10_00142011-001086-41
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Phase I: defining maximum tolerated dose (MTD)

  4 weeks

• Phase II: overall response rate (ORR)

  up to 6 month

Secondary Outcomes (8)

• Complete remission (CR) rate

  up to 12 month

• overall survival (OS)

  up to 12 month

• relapse-free survival (RFS)of the responding patients

  up to 12 month

• number of participants with adverse events as a measure of safety and tolerability

  up to 12 month

• ORR rate of the Flt3-mutated patients versus the Flt3-wildtype patients

  up to 12 month

Study Arms (1)

BIBF 1120

EXPERIMENTAL

Drug: triple kinase inhibitor BIBF1120

Interventions

triple kinase inhibitor BIBF1120 DRUG

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

BIBF 1120

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Muenster: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Universitätsklinikum Münster, Medizinische Klinik und Poliklinik A

Münster, 48149, Germany

Location

Related Publications (2)

• Berdel AF, Koch R, Gerss J, Hentrich M, Peceny R, Bartscht T, Steffen B, Bischoff M, Spiekermann K, Angenendt L, Mikesch JH, Kewitz T, Butterfass-Bahloul T, Serve H, Lenz G, Berdel WE, Krug U, Schliemann C. A randomized phase 2 trial of nintedanib and low-dose cytarabine in elderly patients with acute myeloid leukemia ineligible for intensive chemotherapy. Ann Hematol. 2023 Jan;102(1):63-72. doi: 10.1007/s00277-022-05025-0. Epub 2022 Nov 18.

  PMID: 36399194 DERIVED

• Schliemann C, Gerss J, Wiebe S, Mikesch JH, Knoblauch N, Sauer T, Angenendt L, Kewitz T, Urban M, Butterfass-Bahloul T, Edemir S, Vehring K, Muller-Tidow C, Berdel WE, Krug U. A Phase I Dose Escalation Study of the Triple Angiokinase Inhibitor Nintedanib Combined with Low-Dose Cytarabine in Elderly Patients with Acute Myeloid Leukemia. PLoS One. 2016 Oct 7;11(10):e0164499. doi: 10.1371/journal.pone.0164499. eCollection 2016.

  PMID: 27716819 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Utz Krug, MD

  University Hospital Münster, Medizinische Klinik und Poliklinik A

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2011
• First Posted: December 8, 2011
• Study Start: March 1, 2012
• Primary Completion: November 1, 2014
• Last Updated: December 11, 2013

Record last verified: 2013-12

Locations

DE (1)