Trial of Intensive Chemotherapy With or Without Volasertib in Patients With Newly Diagnosed Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML)
Conditions: official terms
Leukemia - Leukemia, Myeloid - Leukemia, Myeloid, Acute
Conditions: Keywords
Acute Myeloid Leukemia (AML), Volasertib
Study Type
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: Volasertib Type: Drug
Name: Idarubicin Type: Drug
Name: Cytarabine Type: Drug
Name: Etoposide Type: Drug
Name: Daunorubicin Type: Drug
Overall Status
Not yet recruiting
Randomized Phase II Trial of Intensive Chemotherapy With or Without Volasertib (BI 6727) in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Detailed Description
The main trial is a randomized, Phase II, open label multi-centre trial in adult patients with newly diagnosed AML as defined in the inclusion/exclusion criteria.

An initial safety run-in study will be performed administering the study drug volasertib with the two induction regimens DA (daunorubicin, cytarabine) and ICE (idarubicin, cytarabine, etoposide) as well as with high-dose cytarabine consolidation therapy. After establishing the Phase II dose, the randomized Phase II portion of the trial will begin as follows:

Patients will be equally randomized to DA (daunorubicin, cytarabine) and ICE (idarubicin, cytarabine, etoposide) with or without volasertib. Patients achieving CR, CRi or PR will receive a second induction cycle; patients refractory to the first induction cycle will be off-study and followed up in routine care.

Patients in CR/CRi after 2nd induction cycle 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 favourable genetic risk profile and those patients considered ineligible for allogeneic HSCT will receive high-dose cytarabine-based conventional consolidation. All other patients are assigned to allogeneic HSCT.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Patients with suspected diagnosis of acute myeloid leukemia or related precursor neoplasm, or acute leukemia of ambiguous lineage according to the current World Health Organization (WHO) classification

- Genetic assessment in AMLSG central laboratory

- 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 mlU/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). "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 4 weeks 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

- 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.

- Organ insufficiency: creatinine >1.5x upper normal serum level; 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

- Bleeding disorder independent of leukemia

- No consent for biobanking
University Hospital Ulm
Ulm, Germany
Status: Not yet recruiting
Contact: Hartmut Döhner, Prof. Dr.
Start Date
September 2014
Completion Date
June 2020
University of Ulm
University of Ulm
Record processing date processed this data on July 28, 2015 page