Trial Outcomes & Findings for Volasertib in Japanese Patients With Acute Myeloid Leukemia (AML) (NCT NCT01662505)

Last Updated: 2018-07-30

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

19 participants

Primary outcome timeframe

From first administration of trial drug up to 28 days

Results posted on

2018-07-30

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	7	4	8
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	7	4	8

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.
Overall Study Progressive disease	6	1	5
Overall Study Refused cont. medication	0	0	1
Overall Study Not specified above	1	3	2

Baseline Characteristics

Volasertib in Japanese Patients With Acute Myeloid Leukemia (AML)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	V 350 mg n=7 Participants 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.	V 400 mg n=4 Participants 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.	V 450 mg n=8 Participants 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.	Total n=19 Participants Total of all reporting groups
Age, Continuous	72.4 Years STANDARD_DEVIATION 6.0 • n=5 Participants	78.0 Years STANDARD_DEVIATION 5.9 • n=7 Participants	69.1 Years STANDARD_DEVIATION 8.6 • n=5 Participants	72.2 Years STANDARD_DEVIATION 7.7 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants

PRIMARY outcome

Timeframe: From first administration of trial drug up to 28 days

Population: Treated Set

Outcome measures

Outcome measures
Measure	V 350 mg n=7 Participants 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.	V 400 mg n=4 Participants 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.	V 450 mg n=8 Participants 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.
Number of Participants With Dose Limiting Toxicities (DLT) in Cycle 1 for the Determination of the Maximum Tolerated Dose (MTD) of Volasertib	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: From first administration of trial drug up to 28 days

Population: Treated Set

Outcome measures

Outcome measures
Measure	V 350 mg n=8 Participants 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.	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.	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.
MTD of Volasertib	450 milligram (mg)	—	—

SECONDARY outcome

Timeframe: From first administration of trial drug up to 486 days

Population: Treated Set

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.

Outcome measures

Outcome measures
Measure	V 350 mg n=7 Participants 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.	V 400 mg n=4 Participants 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.	V 450 mg n=8 Participants 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.
Best Response by Complete Remission (CR)	1 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: From first administration of trial drug up to 486 days

Population: Treated Set

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 \[100 000/μL\]).

Outcome measures

Outcome measures
Measure	V 350 mg n=7 Participants 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.	V 400 mg n=4 Participants 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.	V 450 mg n=8 Participants 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.
Best Response by CRi	0 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: From first administration of trial drug up to 486 days

Population: Treated Set

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%.

Outcome measures

Outcome measures
Measure	V 350 mg n=7 Participants 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.	V 400 mg n=4 Participants 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.	V 450 mg n=8 Participants 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.
Best Response by PR	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: From first administration of trial drug up to 486 days

Population: Treated Set, patient with remissions

The remission duration is the time from the date of achieving CR or CRi until relapse for patients with documented CR or CRi.

Outcome measures

Outcome measures
Measure	V 350 mg n=1 Participants 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.	V 400 mg n=2 Participants 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.	V 450 mg n=3 Participants 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.
Remission Duration	358.0 Days Standard Deviation NA N=1	72.0 Days Standard Deviation 2.8	170.3 Days Standard Deviation 164.6

Adverse Events

V 350 mg

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

V 400 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

V 450 mg

Serious events: 4 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	V 350 mg n=7 participants at risk 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.	V 400 mg n=4 participants at risk 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.	V 450 mg n=8 participants at risk 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.
Blood and lymphatic system disorders Disseminated intravascular coagulation	14.3% 1/7 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	12.5% 1/8 • From inclusion into the study to 21 days after last drug administration (up to 507 days)
Blood and lymphatic system disorders Febrile neutropenia	28.6% 2/7 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	25.0% 2/8 • From inclusion into the study to 21 days after last drug administration (up to 507 days)
General disorders Pyrexia	0.00% 0/7 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	12.5% 1/8 • From inclusion into the study to 21 days after last drug administration (up to 507 days)
Infections and infestations Bronchopulmonary aspergillosis	14.3% 1/7 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	0.00% 0/8 • From inclusion into the study to 21 days after last drug administration (up to 507 days)
Infections and infestations Infection	14.3% 1/7 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	0.00% 0/8 • From inclusion into the study to 21 days after last drug administration (up to 507 days)
Infections and infestations Sepsis	28.6% 2/7 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	12.5% 1/8 • From inclusion into the study to 21 days after last drug administration (up to 507 days)
Investigations Liver function test abnormal	0.00% 0/7 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	12.5% 1/8 • From inclusion into the study to 21 days after last drug administration (up to 507 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/7 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	12.5% 1/8 • From inclusion into the study to 21 days after last drug administration (up to 507 days)
Nervous system disorders Cerebral infarction	0.00% 0/7 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	0.00% 0/4 • From inclusion into the study to 21 days after last drug administration (up to 507 days)	12.5% 1/8 • From inclusion into the study to 21 days after last drug administration (up to 507 days)

Other adverse events

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Other - Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
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