untreated acute myeloid leukemia patients unfit for an intensive treatment MedDRA version: 19.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Vargatef ® 100 mg Weichkapseln
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: not yet assigned
CAS Number: 928326-83-4
Current Sponsor code: BIBF 1120
Other descriptive name: Varg
Sponsors
University Hospital of Muenster
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with newly diagnosed, relapsed or refractory 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), not eligible for a standard induction and consolidation therapy or for an intensive salvage chemotherapy or an allogeneic stem cell transplantation. • 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 newly diagnosed AML and either 20-30% blasts and/or adverse cytogenetics or myelodysplasia-related changes, the indication for a treatment with 5-azacytidine should be considered prior to inclusion into this 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 6 months after the last administration of study therapy (low-dose cytarabine and/or BIBF 1120).* • Patients at risk for hollow organ perforation (i.e., ulcerative colitis, Crohn`s disease, sigma diverticulitis) should only be included if the potential benefit of the study participation outweighs the risk for perforation in the opinion of the investigator. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 68
Exclusion criteria
Exclusion criteria: • Patients with newly diagnosed AML with either 20-30% bone marrow blasts and/or adverse cytogenetics or myelodysplasia-related changes, which are qualifying for and consenting into a therapy with 5-azacytidine • Known central nervous system manifestation of AML • Inadequate liver function (ALT or AST = 1.5 x ULN) if not caused by leukemic infiltration. In cases of leukemic liver involvement ALT or AST = 2.5 x ULN. • Known chronically active hepatitis C infection or acute Hepatitis • History of acute or chronic pancreatitis • Chronically impaired renal function (creatinine > 1.5 x ULN or GFR 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) • Hypersensitivity to nintedanib, peanut, soya, or any of the components of nintedanib capsules according to the Summary of Product Characteristics (SmPC) of nintedanib • Phase II only: previous therapy with tyrosine kinase inhibitors or angiogenesis inhibitors • Participation in another interventional clinical trial during this trial or within 4 weeks before entry into this trial. There may be exceptions at the discretion of the coordinating investigator.Any severe concomitant condition, which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: phase I: tolerability of BIBF1120 combined with low-dose cytarabine phase II: efficacy of BIBF1120 combined with low-dose cytarabine;Secondary Objective: efficacy of BIBF combined with low-dose cytarabine in predefined subgroups for predefined endpoints identification of biomarkers correlating with the course of the disease under a therapy with BIBF combined with low-dose cytarabine;Primary end point(s): phase I: safety and tolerability of BIBF 1120 combined with low-dose cytarabine phase II: overall survival (OS) of patients treated with low-dose cytarabine plus nintedanib as compared to low-dose cytarabine plus placebo;Timepoint(s) of evaluation of this end point: phase I: after one course Overall survival (OS) (phase II): Time interval from day 1 of study treatment to the day of death. For a patient who is not known to have died by the end of follow-up, observation of OS will be censored on the date the patient was last known to be alive. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • response rate (ORR, consisting of: CR, CRp and CRi as defined by IWG criteria1) of the whole study population • ORR rate of Flt3-mutated patients versus Flt3-wildtype patients and within different cytogenetic risk groups • CR rate of the whole study population • CR rate of the Flt3-mutated patients versus the Flt3-wildtype patients and within different cytogenetic risk groups • overall survival (OS) of the Flt3-mutated patients versus the Flt3-wildtype patients and within different cytogenetic risk groups • relapse-free survival (RFS) of the responding patients • the time to response (CR, CRp or CRi) of the responding patients • the toxicity in the whole study population • the prognostic value of biomarkers indicating the course of disease, including genetic, epigenetic, transcriptional, protein and phosphoprotein markers in leukemic blasts, bone marrow, peripheral blood cells, serum and plasma, and bone marrow microvessel density. • development of biomarkers indicating the course of disease;Timepoint(s) of evaluation of this end point: Complete remission rate (CR rate): at any time point during study participation. Overall response rate (ORR): at any time point during study participation. Overall survival (OS): Time interval from day 1 of study treatment to the day of death. For a patient who is not known to have died by the end of follow-up, observation of OS will be censored on the date the patient was last known to be alive. Relapse-free survival (RFS): Time interval from the first day a leukemia-free state is achieved in patients who achieve a CR / CRi / CRp until relapse or death from any course, whatever occurs first. For a patient who is not known to have died or have relapsed by the end of follow-up, observation of RFS will be censored on the date the patient was last known to be alive and in CR. | — |
Countries
Germany
Contacts
Public ContactStudy Office/Study Coordinator
University Hospital of Muenster
Outcome results
None listed