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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02198482
Other study ID # AMLSG 20-13
Secondary ID 2014-000477-39
Status Terminated
Phase Phase 2
First received July 22, 2014
Last updated February 27, 2018
Start date February 2016
Est. completion date November 2016

Study information

Verified date February 2018
Source University of Ulm
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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)


Description:

The trial is a randomized, Phase II, open label multi-center trial in adult patients with newly diagnosed AML or high-risk MDS as defined in the inclusion/exclusion criteria.

An initial safety run-in study will be performed administering intensive induction therapy consisting of daunorubicin and cytarabine with the study drug volasertib administered prior or after chemotherapy, as well as consolidation therapy consisting of intermediate-dose cytarabine with the study drug volasertib administered prior or after chemotherapy. After establishing the volasertib dose, the randomized Phase II portion of the trial will begin:

Patients will be equally randomized to DA (daunorubicin, cytarabine), V-DA (volasertib administered prior to daunorubicin, cytarabine), and DA-V (volasertib administered after daunorubicin, cytarabine). All patients will receive a second induction cycle with reduced daunorubicin and cytarabine doses. Patients refractory to the first induction cycle and patients not achieving a CR/CRi after two induction cycles will be off-study and followed up.

Patients in CR/CRi after induction therapy will proceed to consolidation therapy. Consolidation will be stratified based on the genetic risk profile (according to ELN criteria) and patient-related factors (e.g., age, HCT-CI, comorbidities, patient wish). Patients with a favorable genetic risk profile and those patients considered ineligible for allogeneic HCT will receive repetitive cycles of consolidation according to initial randomization, either MiDAC, V-MiDAC (volasertib administered prior to cytarabine), or MiDAC-V (volasertib administered after cytarabine). All other patients are assigned to allogeneic HCT.


Recruitment information / eligibility

Status Terminated
Enrollment 6
Est. completion date November 2016
Est. primary completion date November 2016
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

- 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

Exclusion Criteria:

- 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.

- Severe neurological or psychiatric disorder interfering with ability of giving an informed consent

- Known or suspected active alcohol or drug abuse

- Known positive for HIV, active HBV, HCV, or hepatitis A infection

- Hematologic disorder independent of leukemia

- No consent for registration, storage and processing of the individual disease characteristics and course as well as information of the family physician and/or other physicians involved in the treatment of the patient about study participation.

- No consent for biobanking.

- Current participation in any other interventional clinical study within 30 days before the first administration of the investigational product or at any time during the study

- Breast feeding women or women with a positive pregnancy test at Screening visit

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Volasertib

Cytarabine

Daunorubicin

Mitoxantrone


Locations

Country Name City State
Germany Hospital Aschaffenburg Aschaffenburg
Germany Helios Hospital Bad Saarow Bad Saarow
Germany Charite Berlin Campus Virchow Hospital Berlin
Germany Vivantes Hospital Am Urban Berlin
Germany Vivantes Hospital Neukölln Berlin
Germany Knappschaftskrankenhaus Bochum-Langendeer Bochum
Germany University Hospital Bonn Bonn
Germany Community Hospital Braunschweig Braunschweig
Germany Hospital Darmstadt Darmstadt
Germany University Hospital Düsseldorf Düsseldorf
Germany Hospital Essen, Protestant Hospital Essen-Werden Essen
Germany Hospital Esslingen Esslingen
Germany Malteser Hospital St. Franziskus Flensburg
Germany Hospital Frankfurt-Höchst Frankfurt
Germany Medical Care Unit Osthessen Fulda
Germany University Hospital Gießen Gießen
Germany Wilhelm-Anton-Hospital Goch Goch
Germany University Hospital Göttingen Göttingen
Germany Asklepios Hospital Altona Hamburg
Germany University Hospital Hamburg-Eppendorf Hamburg
Germany Hospital Hanau Hanau
Germany Hannover Medical School Hannover
Germany KRH Hospital Siloah-Oststadt-Heidehaus Hannover
Germany SLK-Hospital Heilbronn Heilbronn
Germany Marienhospital Herne Herne
Germany University Hospital des Saarlandes Homburg/Saar
Germany Community Hospital Karlsruhe Karlsruhe
Germany University Hospital Schleswig-Holstein Kiel
Germany Caritas Hospital Lebach Lebach
Germany Hospital Lippe-Lemgo Lemgo
Germany University Hospital Magdeburg Magdeburg
Germany University Hospital Johannes Gutenberg Mainz Mainz
Germany Johannes Wesling Hospital Minden Minden
Germany Hospital rechts der Isar München München
Germany Hospital Schwabing München
Germany Stauferklinikum Schwäbisch-Gmünd Mutlangen
Germany Hospital Oldenburg Oldenburg
Germany Hospital Passau Passau
Germany Diakonie Hospital Stuttgart Stuttgart
Germany Hospital Stuttgart Stuttgart
Germany Hospital Traunstein Traunstein
Germany Hospital Barmherzige Brüder Trier Trier
Germany Mutterhaus der Borromäerinnen Trier
Germany University Hospital Tübingen Tübingen
Germany University Hospital Ulm Ulm

Sponsors (1)

Lead Sponsor Collaborator
University of Ulm

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary Rate of complete remission (CR) and CR with incomplete blood count recovery (CRi) 2 months
Secondary Cumulative incidence of relapse 4 years
Secondary Cumulative incidence of death 4 years
Secondary Relapse-free survival 4 years
Secondary Event-free survival 4 years
Secondary Overall survival 4 years
Secondary Incidence and intensity of adverse events 8 months
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