Leukemia, Myeloid, Acute
Conditions
Brief summary
To investigate safety, tolerability, maximum tolerated dose of volasertib in Japanese patients with AML
Interventions
DRUGVolasertib
Patient to receive volasertib
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with diagnosis of AML (except for acute promyelocytic leukemia, APL) according to the World Health Organization definition and with one of the following features at screening * Relapsed or refractory AML * Untreated AML patients not considered to be suitable for standard induction therapy according to investigator's judgement 2. Male or female patients of age \>/= 18 years at the time of informed consent 3. Eastern Cooperative Oncology Group performance status score 0 - 2 at screening 4. Signed written informed consent consistent with Japanese Good Clinical Practice.
Exclusion criteria
1. Patients with APL 2. Patients in the third or later relapse 3. Prior stem cell transplantation 4. Treatment with systemic therapy for the primary disease (including an investigational drug) within 14 days before the first dose of volasertib with the exception of hydroxyurea, or lack of recovery from any acute toxicities or clinically significant adverse events pertinent to the prior systemic therapy 5. Treatment with gemtuzumab ozogamicin within 6 weeks before the first dose of volasertib 6. Concomitant medication/treatment with anti-leukemic chemotherapy (systemic or intrathecal), radiotherapy, immunotherapy, or any investigational agent while receiving study treatment 7. Other malignancy requiring treatment at the time of screening 8. Clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukemic CNS involvement or requiring treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLT) in Cycle 1 for the Determination of the Maximum Tolerated Dose (MTD) of Volasertib | From first administration of trial drug up to 28 days | Primary objective for this trial was to identify the MTD of volasertib. The MTD was defined as the highest dose level at which DLTs were reported in at most 2 in 6 evaluable patients during cycle 1. In this outcome measure the number of participants with DLTs in cycle 1 is presented. |
| MTD of Volasertib | From first administration of trial drug up to 28 days | Primary objective for this trial was to identify the MTD of volasertib. The MTD was defined as the highest dose level at which DLTs were reported in at most 2 in 6 evaluable patients during cycle 1. In this outcome measure the MTD is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Response by Complete Remission (CR) | From first administration of trial drug up to 486 days | The secondary outcome best response will be presented by the CR, CR with incomplete blood count recovery (CRi) and partial remission (PR). In this outcome measure the CR will be presented. The criteria for the CR are: Bone marrow blasts less than 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) \>1.0 × 10\^9/Litre (L) (1000/microlitre (μL)); platelet count \>100 × 10\^9/L (100 000/μL); independence of red cell transfusions. |
| Best Response by CRi | From first administration of trial drug up to 486 days | The secondary outcome best response will be presented by the CR, CRi and PR. In this outcome measure the CRi will be presented. The criteria for the CRi are: All CR criteria are met except for residual neutropenia (\<1.0 × 10\^9/L \[1000/μL\]) or thrombocytopenia (\<100 × 10\^9/L \[100 000/μL\]). |
| Best Response by PR | From first administration of trial drug up to 486 days | The secondary outcome best response will be presented by the CR, CRi and PR. In this outcome measure the PR is presented. The criteria for the PR are: All haematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%. |
| Remission Duration | From first administration of trial drug up to 486 days | The remission duration is the time from the date of achieving CR or CRi until relapse for patients with documented CR or CRi. |
Countries
Japan
Participant flow
Pre-assignment details
Patients with written informed consent underwent screening within (≤) 14 days before starting the volasertib treatment. Eligible patients were enrolled and treated as soon as possible or within (≤)14 days after obtaining informed consent.
Participants by arm
| Arm | Count |
|---|---|
| V 350 mg Patients received 350 milligram (mg) of volasertib (V) as monotherapy on Days 1 and 15 of a 28-day cycle via intravenous (i.v.) drip infusion over 2 hours. | 7 |
| V 400 mg Patients received 400 mg of volasertib as monotherapy on Days 1 and 15 of a 28-day cycle via i.v. drip infusion over 2 hours. | 4 |
| V 450 mg Patients received 450 mg of volasertib as monotherapy on Days 1 and 15 of a 28-day cycle via i.v. drip infusion over 2 hours. | 8 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Not specified above | 1 | 3 | 2 |
| Overall Study | Progressive disease | 6 | 1 | 5 |
| Overall Study | Refused cont. medication | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | V 350 mg | V 400 mg | V 450 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 72.4 Years STANDARD_DEVIATION 6 | 78.0 Years STANDARD_DEVIATION 5.9 | 69.1 Years STANDARD_DEVIATION 8.6 | 72.2 Years STANDARD_DEVIATION 7.7 |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 4 / 4 | 8 / 8 |
| serious Total, serious adverse events | 3 / 7 | 0 / 4 | 4 / 8 |
Outcome results
Primary
MTD of Volasertib
Primary objective for this trial was to identify the MTD of volasertib. The MTD was defined as the highest dose level at which DLTs were reported in at most 2 in 6 evaluable patients during cycle 1. In this outcome measure the MTD is presented.
Time frame: From first administration of trial drug up to 28 days
Population: Treated Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V 350 mg | MTD of Volasertib | 450 milligram (mg) |
Primary
Number of Participants With Dose Limiting Toxicities (DLT) in Cycle 1 for the Determination of the Maximum Tolerated Dose (MTD) of Volasertib
Primary objective for this trial was to identify the MTD of volasertib. The MTD was defined as the highest dose level at which DLTs were reported in at most 2 in 6 evaluable patients during cycle 1. In this outcome measure the number of participants with DLTs in cycle 1 is presented.
Time frame: From first administration of trial drug up to 28 days
Population: Treated Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V 350 mg | Number of Participants With Dose Limiting Toxicities (DLT) in Cycle 1 for the Determination of the Maximum Tolerated Dose (MTD) of Volasertib | 0 Participants |
| V 400 mg | Number of Participants With Dose Limiting Toxicities (DLT) in Cycle 1 for the Determination of the Maximum Tolerated Dose (MTD) of Volasertib | 0 Participants |
| V 450 mg | Number of Participants With Dose Limiting Toxicities (DLT) in Cycle 1 for the Determination of the Maximum Tolerated Dose (MTD) of Volasertib | 1 Participants |
Secondary
Best Response by Complete Remission (CR)
The secondary outcome best response will be presented by the CR, CR with incomplete blood count recovery (CRi) and partial remission (PR). In this outcome measure the CR will be presented. The criteria for the CR are: Bone marrow blasts less than 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) \>1.0 × 10\^9/Litre (L) (1000/microlitre (μL)); platelet count \>100 × 10\^9/L (100 000/μL); independence of red cell transfusions.
Time frame: From first administration of trial drug up to 486 days
Population: Treated Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V 350 mg | Best Response by Complete Remission (CR) | 1 Participants |
| V 400 mg | Best Response by Complete Remission (CR) | 0 Participants |
| V 450 mg | Best Response by Complete Remission (CR) | 2 Participants |
Secondary
Best Response by CRi
The secondary outcome best response will be presented by the CR, CRi and PR. In this outcome measure the CRi will be presented. The criteria for the CRi are: All CR criteria are met except for residual neutropenia (\<1.0 × 10\^9/L \[1000/μL\]) or thrombocytopenia (\<100 × 10\^9/L \[100 000/μL\]).
Time frame: From first administration of trial drug up to 486 days
Population: Treated Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V 350 mg | Best Response by CRi | 0 Participants |
| V 400 mg | Best Response by CRi | 2 Participants |
| V 450 mg | Best Response by CRi | 1 Participants |
Secondary
Best Response by PR
The secondary outcome best response will be presented by the CR, CRi and PR. In this outcome measure the PR is presented. The criteria for the PR are: All haematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.
Time frame: From first administration of trial drug up to 486 days
Population: Treated Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V 350 mg | Best Response by PR | 0 Participants |
| V 400 mg | Best Response by PR | 0 Participants |
| V 450 mg | Best Response by PR | 1 Participants |
Secondary
Remission Duration
The remission duration is the time from the date of achieving CR or CRi until relapse for patients with documented CR or CRi.
Time frame: From first administration of trial drug up to 486 days
Population: Treated Set, patient with remissions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| V 350 mg | Remission Duration | 358.0 Days | — |
| V 400 mg | Remission Duration | 72.0 Days | Standard Deviation 2.8 |
| V 450 mg | Remission Duration | 170.3 Days | Standard Deviation 164.6 |