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Acute Myeloid Leukemia (AML)Phase 2NCT02198482

Trial of Intensive Chemotherapy With or Without Volasertib in Patients With Newly Diagnosed High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)

A Phase 2 study testing Volasertib, Cytarabine and Daunorubicin in people with Acute Myeloid Leukemia (AML) and High-risk Myelodysplastic Syndrome (MDS), run by University of Ulm at 45 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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) Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Volasertib, Cytarabine and Daunorubicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
45 sitesGermany
Study dates
Feb 2016to Nov 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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:
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  • 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

Trial locations and contacts

45 sites in 1 country.

45 sites in 1 country

Germany45 sites

  • Hospital Aschaffenburg

    Aschaffenburg, 63739

  • Helios Hospital Bad Saarow

    Bad Saarow, 15526

  • Vivantes Hospital Am Urban

    Berlin, 10967

  • Vivantes Hospital Neukölln

    Berlin, 12351

  • Charite Berlin Campus Virchow Hospital

    Berlin, 13353

  • Knappschaftskrankenhaus Bochum-Langendeer

    Bochum, 44892

  • University Hospital Bonn

    Bonn, 53105

  • Community Hospital Braunschweig

    Braunschweig, 38114

  • Hospital Darmstadt

    Darmstadt, 64283

  • University Hospital Düsseldorf

    Düsseldorf, 40225

  • Hospital Essen, Protestant Hospital Essen-Werden

    Essen, 45239

  • Hospital Esslingen

    Esslingen am Neckar, 73730

  • Malteser Hospital St. Franziskus

    Flensburg, 24939

  • Hospital Frankfurt-Höchst

    Frankfurt, 65929

  • Medical Care Unit Osthessen

    Fulda, 36043

  • University Hospital Gießen

    Giessen, 35392

  • Wilhelm-Anton-Hospital Goch

    Goch, 47574

  • University Hospital Göttingen

    Göttingen, 37075

  • University Hospital Hamburg-Eppendorf

    Hamburg, 20246

  • Asklepios Hospital Altona

    Hamburg, 22763

  • Hospital Hanau

    Hanau, 63450

  • KRH Hospital Siloah-Oststadt-Heidehaus

    Hanover, 30459

  • Hannover Medical School

    Hanover, 30625

  • SLK-Hospital Heilbronn

    Heilbronn, 74078

  • Marienhospital Herne

    Herne, 44625

  • University Hospital des Saarlandes

    Homburg/Saar, 66421

  • Community Hospital Karlsruhe

    Karlsruhe, 76133

  • University Hospital Schleswig-Holstein

    Kiel, 24105

  • Caritas Hospital Lebach

    Lebach, 66822

  • Hospital Lippe-Lemgo

    Lemgo, 32657

  • University Hospital Magdeburg

    Magdeburg, 39120

  • University Hospital Johannes Gutenberg Mainz

    Mainz, 55131

  • Johannes Wesling Hospital Minden

    Minden, 32429

  • Hospital Schwabing

    München, 80804

  • Hospital rechts der Isar München

    München, 81675

  • Stauferklinikum Schwäbisch-Gmünd

    Mutlangen, 73557

  • Hospital Oldenburg

    Oldenburg, 26133

  • Hospital Passau

    Passau, 94032

  • Hospital Stuttgart

    Stuttgart, 70174

  • Diakonie Hospital Stuttgart

    Stuttgart, 70176

  • Hospital Traunstein

    Traunstein, 83278

  • Mutterhaus der Borromäerinnen

    Trier, 54290

  • Hospital Barmherzige Brüder Trier

    Trier, 54292

  • University Hospital Tübingen

    Tübingen, 72076

  • University Hospital Ulm

    Ulm, 89081

Other trials in Germany

About this study

Official title: 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)

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)

Read the detailed 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.

Being tested
Volasertib, Cytarabine, Daunorubicin, Mitoxantrone
Keywords
Acute Myeloid Leukemia (AML), Volasertib, High-risk Myelodysplastic Syndrome (MDS)
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VolasertibDrug

  • CytarabineDrug

    Also called ARA-cell

  • DaunorubicinDrug

    Also called Daunoplastin

  • MitoxantroneDrug

    Also called Novantron

Study groups in NCT02198482
Study groupRoleWhat they receive
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.
Receives: Drug: Cytarabine; Drug: Daunorubicin; Drug: Mitoxantrone
Volasertib, Daunorubicin, CytarabineExperimentalVDA 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.
Receives: Drug: Volasertib; Drug: Cytarabine; Drug: Daunorubicin; Drug: Mitoxantrone
Daunorubicin, Cytarabine, VolasertibExperimentalDAV 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.
Receives: Drug: Volasertib; Drug: Cytarabine; Drug: Daunorubicin; Drug: Mitoxantrone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of complete remission (CR) and CR with incomplete blood count recovery (CRi)

    Measured: 2 months

Secondary outcomes (6)

  1. Cumulative incidence of relapse

    Measured: 4 years

  2. Cumulative incidence of death

    Measured: 4 years

  3. Relapse-free survival

    Measured: 4 years

  4. Event-free survival

    Measured: 4 years

  5. Overall survival

    Measured: 4 years

  6. Incidence and intensity of adverse events

    Measured: 8 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jul 2014 (estimated)
  2. Study startFeb 2016
  3. Primary completionNov 2016
  4. Study completionNov 2016

Why it stopped: development program of study drug volasertib was stopped by Boehringer Ingelheim due to manufacturing problems

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02198482
Sponsor's protocol ID
AMLSG 20-13
Other IDs
2014-000477-39, 2014
Status last verified
Feb 2018
First submitted
22 Jul 2014
Last updated
28 Feb 2018
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Volasertib, Cytarabine and Daunorubicin in people with Acute Myeloid Leukemia (AML) and High-risk Myelodysplastic Syndrome (MDS), run by University of Ulm at 45 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: development program of study drug volasertib was stopped by Boehringer Ingelheim due to manufacturing problems). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of complete remission (CR) and CR with incomplete blood count recovery (CRi) (time frame: 2 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02198482.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2018.

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