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- Klinische proef NCT01488344
Phase I/II Trial: BIBF 1120 Added to Low-dose Cytarabine in Elderly Patients With Acute Myeloid Leukemia (AML)
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
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).
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Studietype
Inschrijving (Verwacht)
Fase
- Fase 2
- Fase 1
Contacten en locaties
Studie Locaties
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Münster, Duitsland, 48149
- Universitätsklinikum Münster, Medizinische Klinik und Poliklinik A
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: BIBF 1120
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triple kinase inhibitor BIBF1120 is given in addition to low-dose cytarabine
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
|---|---|
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Phase I: defining maximum tolerated dose (MTD)
Tijdsspanne: 4 weeks
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4 weeks
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Phase II: overall response rate (ORR)
Tijdsspanne: up to 6 month
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up to 6 month
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Complete remission (CR) rate
Tijdsspanne: up to 12 month
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up to 12 month
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overall survival (OS)
Tijdsspanne: up to 12 month
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up to 12 month
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relapse-free survival (RFS)of the responding patients
Tijdsspanne: up to 12 month
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up to 12 month
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number of participants with adverse events as a measure of safety and tolerability
Tijdsspanne: up to 12 month
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up to 12 month
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ORR rate of the Flt3-mutated patients versus the Flt3-wildtype patients
Tijdsspanne: up to 12 month
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up to 12 month
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CR rate of the Flt3-mutated patients versus the Flt3-wildtype patients
Tijdsspanne: up to 12 month
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up to 12 month
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OS of the Flt3-mutated patients versus the Flt3-wildtype patients
Tijdsspanne: up to 12 month
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up to 12 month
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time to response (CR, CRp, CRi) of the responding patients
Tijdsspanne: up to 12 month
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CRp = complete remission with incomplete platelet recovery CRi = complete remission with incomplete neutrophil recovery
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up to 12 month
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Medewerkers en onderzoekers
Sponsor
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Utz Krug, MD, University Hospital Münster, Medizinische Klinik und Poliklinik A
Publicaties en nuttige links
Algemene publicaties
- 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.
- 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.
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Verwacht)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- UKM10_0014
- 2011-001086-41 (EudraCT-nummer)
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