Study Stopped
development program of study drug volasertib was stopped by Boehringer Ingelheim due to manufacturing problems
Trial of Intensive Chemotherapy With or Without Volasertib in Patients With Newly Diagnosed High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)
Dose Finding Safety Run-in Phase Followed by a Randomized Phase II Trial of Intensive Chemotherapy With or Without Volasertib (BI 6727) Administered Prior or After Chemotherapy in Patients With Newly Diagnosed High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)
2 other identifiers
interventional
6
1 country
45
Brief Summary
Randomized Phase II Trial of Intensive Chemotherapy With or Without Volasertib (BI 6727) in Patients With Newly Diagnosed High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Feb 2016
Shorter than P25 for phase_2
45 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 22, 2014
CompletedFirst Posted
Study publicly available on registry
July 23, 2014
CompletedStudy Start
First participant enrolled
February 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2016
CompletedFebruary 28, 2018
February 1, 2018
9 months
July 22, 2014
February 27, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Rate of complete remission (CR) and CR with incomplete blood count recovery (CRi)
2 months
Secondary Outcomes (6)
Cumulative incidence of relapse
4 years
Cumulative incidence of death
4 years
Relapse-free survival
4 years
Event-free survival
4 years
Overall survival
4 years
- +1 more secondary outcomes
Study Arms (3)
Daunorubicin, Cytarabine (DA)
ACTIVE COMPARATORDA Induction I: * Daunorubicin 60 mg/m² i.v., d 1-3 * Cytarabine 100 mg/m² cont. i.v., d 1-7 Induction II: * Daunorubicin 50 mg/m² i.v. d 1-3 * Cytarabine 100 mg/m² cont. i.v., d 1-5 Consolidation therapy: Patients with genetic favourable risk and those patients not eligible for allogeneic HSCT due to comorbidities, high HCT-CI or patient wish will proceed to 3 cycles of age-adapted consolidation therapy with mitoxantrone and intermediate-dose cytarabine (MiDAC). * Mitoxantrone Younger adults (18 to 60 yrs): 10 mg/m2 by i.v. on day 1. Elderly patients (\>60 yrs): 8 mg/m2 by i.v. infusion on day 1. * Intermediate-dose cytarabine: Younger adults (18 to 60 yrs): 1500 mg/m2 q12h on days 1-3 Elderly patients (\>60 yrs): 1000 mg/m2 q12h on days 1-3 An allogeneic HSCT is intended for patients with intermediate I/II and adverse-risk genetics. Optionally, one cycle of consolidation with MiDAC may be given prior to alloHSCT.
Volasertib, Daunorubicin, Cytarabine
EXPERIMENTALVDA Induction I * Volasertib i.v., d1 * Daunorubicin 60 mg/m² i.v., d 2-4 * Cytarabine 100 mg/m² cont. i.v., d 2-8 Induction II * Volasertib i.v., d1 * Daunorubicin 50 mg/m² i.v. d 2-4 * Cytarabine 100 mg/m² cont. i.v., d 2-6 Consolidation therapy: Patients with genetic favourable risk and those patients not eligible for allogeneic HSCT will proceed to 3 cycles of age-adapted consolidation therapy with mitoxantrone and intermediate-dose cytarabine in combination with Volasertib (V-MiDAC). * Volasertib i.v., d1 * Mitoxantrone Younger adults (18 to 60 yrs): 10 mg/m2 by i.v. on day 2. Elderly patients (\>60 yrs): 8 mg/m2 by i.v. on day 2. * Intermediate-dose cytarabine: Younger adults (18 to 60 yrs): 1500 mg/m2 q12h on days 2-4 Elderly patients (\>60 yrs): 1000 mg/m2 q12h on days 2-4 An allogeneic HSCT is intended for patients with intermediate I/II and adverse-risk genetics. Optionally, one cycle of consolidation with V-MiDAC may be given prior to alloHSCT.
Daunorubicin, Cytarabine, Volasertib
EXPERIMENTALDAV Induction I * Volasertib i.v., d7 * Daunorubicin 60 mg/m² i.v., d 1-3 * Cytarabine 100 mg/m² i.v., d 1-7 Induction II * Volasertib i.v., d5 * Daunorubicin 50 mg/m² i.v. d 1-3 * Cytarabine 100 mg/m² cont. i.v., d 1-5 Consolidation therapy: Patients with genetic fav. risk and those patients not eligible for alloHSCT will proceed to 3 cycles of age-adapted consolidation therapy with mitoxantrone and intermediate-dose cytarabine in combination with Volasertib (MiDAC-V). * Volasertib i.v., d4 * Mitoxantrone Younger adults (18 to 60 yrs): 10 mg/m2 by i.v. on day 1. Elderly patients (\>60 yrs): 8 mg/m2 by i.v. on day 1. * Intermediate-dose cytarabine: Younger adults (18 to 60 yrs): 1500 mg/m2 q12h on days 1-3 Elderly patients (\>60 yrs): 1000 mg/m2 q12h on days 1-3 An allogeneic HSCT is intended for patients with intermediate I/II and adverse-risk genetics. Optionally, one cycle of consolidation with MiDAC-V may be given prior to alloHSCT.
Interventions
Eligibility Criteria
You may qualify if:
- Patients with confirmed diagnosis of acute myeloid leukemia (AML) or related precursor neoplasm, or acute leukemia of ambiguous lineage according to the current World Health Organization (WHO) classification, or patients with myelodysplastic syndrome (MDS) classified as refractory anemia with excess blasts-2 (RAEB-2)
- Consent for a genetic assessment in AMLSG central laboratory
- Patients considered eligible for intensive chemotherapy
- ECOG performance status of ≤ 2
- Age \>= 18; there is no upper age limit
- No prior chemotherapy for acute leukemia except hydroxyurea for up to 5 days during the diagnostic screening phase; patients may have received prior therapy for myelodysplastic syndrome.
- Non-pregnant and non-nursing. Due to the teratogenic potential of volasertib in humans, pregnant or nursing patients may not be enrolled. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to registration. Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control - one highly effective method (e.g., IUD, hormonal, tubal ligation, or partner's vasectomy), and one additional effective method (e.g., latex condom, diaphragm, or cervical cap) for 6 months after therapy is stopped. "Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months.
- Men must agree not to father a child and must use a latex condom during any sexual contact with women of childbearing potential while receiving therapy and for 6 months after therapy is stopped, even if they have undergone a successful vasectomy
- Signed written informed consent
You may not qualify if:
- Patients with acute promyelocytic leukemia exhibiting t(15;17)(q22;q12); PML-RARA, or with variant translocations
- Prior treatment with volasertib or any other PLK1 inhibitor
- Performance status WHO \>2 (see Appendix I)
- Patients with ejection fraction \<50% by echocardiography within 14 days of day 1
- QTcF prolongation \>470 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome). The QTcF will be calculated as the mean of 3 ECGs taken at screening.
- Any clinically significant, advanced or unstable disease or history of that may interfere with primary or secondary variable evaluations or put the patient at special risk, such as:
- creatinine \>1.5x upper normal serum level;
- total bilirubin, AST or AP \>2.5x upper normal serum level;
- heart failure NYHA III/IV,
- uncontrolled hypertension,
- unstable angina,
- serious cardiac arrhythmia;
- severe obstructive or restrictive ventilation disorder
- uncontrolled infection
- Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy, if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within one year.
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (45)
Hospital Aschaffenburg
Aschaffenburg, 63739, Germany
Helios Hospital Bad Saarow
Bad Saarow, 15526, Germany
Vivantes Hospital Am Urban
Berlin, 10967, Germany
Vivantes Hospital Neukölln
Berlin, 12351, Germany
Charite Berlin Campus Virchow Hospital
Berlin, 13353, Germany
Knappschaftskrankenhaus Bochum-Langendeer
Bochum, 44892, Germany
University Hospital Bonn
Bonn, 53105, Germany
Community Hospital Braunschweig
Braunschweig, 38114, Germany
Hospital Darmstadt
Darmstadt, 64283, Germany
University Hospital Düsseldorf
Düsseldorf, 40225, Germany
Hospital Essen, Protestant Hospital Essen-Werden
Essen, 45239, Germany
Hospital Esslingen
Esslingen am Neckar, 73730, Germany
Malteser Hospital St. Franziskus
Flensburg, 24939, Germany
Hospital Frankfurt-Höchst
Frankfurt, 65929, Germany
Medical Care Unit Osthessen
Fulda, 36043, Germany
University Hospital Gießen
Giessen, 35392, Germany
Wilhelm-Anton-Hospital Goch
Goch, 47574, Germany
University Hospital Göttingen
Göttingen, 37075, Germany
University Hospital Hamburg-Eppendorf
Hamburg, 20246, Germany
Asklepios Hospital Altona
Hamburg, 22763, Germany
Hospital Hanau
Hanau, 63450, Germany
KRH Hospital Siloah-Oststadt-Heidehaus
Hanover, 30459, Germany
Hannover Medical School
Hanover, 30625, Germany
SLK-Hospital Heilbronn
Heilbronn, 74078, Germany
Marienhospital Herne
Herne, 44625, Germany
University Hospital des Saarlandes
Homburg/Saar, 66421, Germany
Community Hospital Karlsruhe
Karlsruhe, 76133, Germany
University Hospital Schleswig-Holstein
Kiel, 24105, Germany
Caritas Hospital Lebach
Lebach, 66822, Germany
Hospital Lippe-Lemgo
Lemgo, 32657, Germany
University Hospital Magdeburg
Magdeburg, 39120, Germany
University Hospital Johannes Gutenberg Mainz
Mainz, 55131, Germany
Johannes Wesling Hospital Minden
Minden, 32429, Germany
Stauferklinikum Schwäbisch-Gmünd
Mutlangen, 73557, Germany
Hospital Schwabing
München, 80804, Germany
Hospital rechts der Isar München
München, 81675, Germany
Hospital Oldenburg
Oldenburg, 26133, Germany
Hospital Passau
Passau, 94032, Germany
Hospital Stuttgart
Stuttgart, 70174, Germany
Diakonie Hospital Stuttgart
Stuttgart, 70176, Germany
Hospital Traunstein
Traunstein, 83278, Germany
Mutterhaus der Borromäerinnen
Trier, 54290, Germany
Hospital Barmherzige Brüder Trier
Trier, 54292, Germany
University Hospital Tübingen
Tübingen, 72076, Germany
University Hospital Ulm
Ulm, 89081, Germany
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Hartmut Döhner, Prof. Dr.
AMLSG Clinical Trials Office
- STUDY CHAIR
Peter Paschka, MD
University Hospital Ulm
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Prof. Dr.
Study Record Dates
First Submitted
July 22, 2014
First Posted
July 23, 2014
Study Start
February 1, 2016
Primary Completion
November 1, 2016
Study Completion
November 1, 2016
Last Updated
February 28, 2018
Record last verified: 2018-02