Leukemia, Myeloid, AcutePhase 1NCT02003573

Volasertib + Decitabine in Patients With Acute Myeloid Leukemia (AML)

A Phase 1 study testing decitabine iv and volasertib iv infusion in people with Leukemia, Myeloid, Acute, run by Boehringer Ingelheim at 3 sites in United States.

Terminated

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

Official record

Search all trials

Trial summary

Dose Escalation (MTD Finding) Phase: To investigate the maximum tolerated dose (MTD), safety and pharmacokinetics of different volasertib administration schedules in combination with decitabine in previously untreated AML patients >= 65 years of age who are considered ineligible for standard intensive therapy, or… Read more about this study

Who is it for?: Ages 65 years and older
Conditions the study is for: Leukemia, Myeloid, Acute
What is being tested?: decitabine iv and volasertib iv infusion
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 3 sitesUnited States
Study dates: 29 Jan 2014to 15 May 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 65 years and older
All sexes
No healthy volunteers
Older adult

Who may be able to join

Dose Escalation Phase: patients with previously untreated AML, relapsed or refractory AML regardless of prior treatment status.
MTD Extension Phase: previously untreated AML (prior treatment for Myelodysplastic Syndrome(MDS) is allowed).
Age >= 65 years.
Previously untreated patients must be ineligible for receiving standard intensive therapy at the time of enrolment, in the opinion of the investigator and based on documented medical reasons.
Histologically or cytologically confirmed AML (except for APL, FAB (French-American-British)subtype M3) according to the World Health Organisation classification.
Eastern co-operative oncology group (ECOG) performance score =< 1 at screening.
Signed and dated written informed consent by start date of Screening Visit in accordance with Good Clinical Practice and local legislation.

Who cannot join

MTD Extension Phase: Prior chemotherapy for AML (except for hydroxyurea). Patients can receive treatment with hydroxyurea in order to reduce high White Blood Cells count for no more than 28 days (cumulative); discontinuation of hydroxyurea at least one day prior to the study treatment is required. Please note that any prior therapy for MDS is allowed.
Acute promyelocytic leukemia (APL, FAB subtype M3), according to World Health Organisation classification.
Hypersensitivity to the trial drugs.
Other malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer).
Known clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukemic CNS involvement.
QTcF (QT interval corrected for heart rate by the Fridericia formula) > 470 ms, calculated as the mean value of the triplicates taken at least 2 minutes apart at baseline or QTcF prolongation deemed clinically relevant by the investigator.

Show all 20Show fewer

Baseline Left Ventricular Ejection Fraction of < 45% or below the lower limit of institutional normal range.
Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 2.5 x the upper limit of normal (ULN). Patients with elevated liver enzyme(s) due to leukemic involvement are allowed up to = 5 x the ULN.
Total bilirubin > 1.5 x ULN. For patients with Gilbert's syndrome or elevation due to hepatic infiltrate, total bilirubin must be <4 x ULN.
Creatinine clearance (CLcr) < 30 ml/min (estimated creatinine clearance by the Cockcroft-Gault (C-G) equation.
Severe illness or organ dysfunction involving the kidneys, liver or other organ system, including active uncontrolled infection, which in the opinion of the investigator precludes treatment with decitabine or would interfere with the evaluation of the safety of the study treatment.
Presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) Classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to study entry.
Significant concurrent psychiatric disorder or social situation that according to the investigator's judgment would compromise patient's safety or compliance, interfere with consent, study participation, or interpretation of study results.
Patients with a systemic fungal, bacterial, viral, or other infection that is not controlled.
Contraindications for decitabine treatment according to the manufacturer's prescribing information provided in the Investigator Site File
Female patients of childbearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial and for a minimum of 6 months after completion of study treatment.
Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second medically acceptable method of contraception during the trial and for a minimum of 6 months after completion of study treatment.
Pregnant or breast feeding patients.
Treatment with any investigational drug within 2 weeks of administration of first study medication dose or within less than five half -lives of the investigational drug before treatment with the present trial drug, whichever is shorter, and / or persistence of toxicities of prior anti-leukemic therapies which are deemed clinically relevant.
Prior treatment with a Plk inhibitor such as volasertib or treatment in a clinical trial using a Plk inhibitory compound.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Yale Cancer Center
New Haven, Connecticut, 06510
Washington School of Medicine
St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: An Open Label, Phase I, Dose Escalation Trial to Investigate the Maximum Tolerated Dose, Safety, Pharmacokinetics, and Efficacy of Volasertib in Combination With Decitabine in Patients >= 65 Years With Acute Myeloid Leukemia

MTD Extension Phase: To collect additional data on safety, efficacy and pharmacokinetics of volasertib in combination with decitabine in previously untreated patients with AML >= 65 years of age and considered ineligible for standard intensive therapy.

Conditions: Leukemia, Myeloid, Acute
Being tested: decitabine iv, volasertib iv infusion
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.

decitabine ivDrug
decitabine iv fixed dose
volasertib iv infusionDrug
volasertib iv infusion (Body Surface Area (BSA) based dosing)

Study groups in NCT02003573
Study group	Role	What they receive
volasertib + decitabine	Experimental	dose escalation and MTD (Maximum Tolerated Dose) Extension (Note: Decitabine is a Backbone Treatment and Volasertib is Investigational Medicinal Product (IMP)) Receives: Drug: decitabine iv; Drug: volasertib iv infusion

What is being measured

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

Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in Cycle 1
The primary objective of the dose-escalation part of this study was to determine the MTD of volasertib in combination with decitabine. The MTD was to be identified based on the DLT information collected during the first treatment cycle of each dosing schedule. DLT was defined as a non-haematological drug-related toxicity of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3.
The MTD corresponded to the highest dose of volasertib and decitabine at which the incidence of DLT was ≤17% (i.e. 1/6 patients) during Cycle 1.
Measured: 4 weeks
Number of Subjects With Dose Limiting Toxicities (DLT) in Cycle 1
Number of subjects with Dose Limiting Toxicities (DLT) in Cycle 1 is presented
Measured: 4 weeks

Timeline

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

29 Jan 201415 May 2016

First posted6 Dec 2013 (estimated)
Study start29 Jan 2014
Primary completion6 Jan 2015
Study completion15 May 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1
Primary purpose: Treatment
Intervention model: Sequential
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02003573
Sponsor's protocol ID: 1230.30
Other IDs: 2013-001752-36
Status last verified: Aug 2018
First submitted: 3 Dec 2013
Last updated: 31 Jan 2019
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome

All Leukemia, Myeloid, Acute trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open Label, Phase I, Dose Escalation Trial to Investigate the Maximum Tolerated Dose, Safety, Pharmacokinetics, and Efficacy of Volasertib in Combination With Decitabine in Patients >= 65 Years With Acute Myeloid Leukemia
ClinicalTrials.gov ID: NCT02003573
Acronym / sponsor ID: 1230.30
Conditions: Leukemia, Myeloid, Acute
Phase: Phase 1
Study type: Interventional
Recruitment status: Terminated
Enrolment: 13 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 29 Jan 2014 (actual)
Primary completion: 6 Jan 2015 (actual)
Study completion: 15 May 2016 (actual)
First posted: 6 Dec 2013 (estimated)
Results: Posted 31 Jan 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Intervention model: Sequential
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
volasertib + decitabine	Experimental	Drug: decitabine iv, Drug: volasertib iv infusiondose escalation and MTD (Maximum Tolerated Dose) Extension (Note: Decitabine is a Backbone Treatment and Volasertib is Investigational Medicinal Product (IMP))

Who may qualify

Ages: 65 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Older adult

Key inclusion criteria (7 listed)

Dose Escalation Phase: patients with previously untreated AML, relapsed or refractory AML regardless of prior treatment status.
MTD Extension Phase: previously untreated AML (prior treatment for Myelodysplastic Syndrome(MDS) is allowed).
Age >= 65 years.
Previously untreated patients must be ineligible for receiving standard intensive therapy at the time of enrolment, in the opinion of the investigator and based on documented medical reasons.
Histologically or cytologically confirmed AML (except for APL, FAB (French-American-British)subtype M3) according to the World Health Organisation classification.

Key exclusion criteria (20 listed)

MTD Extension Phase: Prior chemotherapy for AML (except for hydroxyurea). Patients can receive treatment with hydroxyurea in order to reduce high White Blood Cells count for no more than 28 days (cumulative); discontinuation of hydroxyurea at least one day prior to the study treatment is required. Please note that any prior therapy for MDS is allowed.
Acute promyelocytic leukemia (APL, FAB subtype M3), according to World Health Organisation classification.
Hypersensitivity to the trial drugs.
Other malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer).
Known clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukemic CNS involvement.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
decitabine ivdecitabine iv fixed dose	Drug	volasertib + decitabine
volasertib iv infusionvolasertib iv infusion (Body Surface Area (BSA) based dosing)	Drug	volasertib + decitabine

Primary outcome

Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in Cycle 1
Time frame: 4 weeks
The primary objective of the dose-escalation part of this study was to determine the MTD of volasertib in combination with decitabine. The MTD was to be identified based on the DLT information collected during the first treatment cycle of each dosing schedule. DLT was defined as a non-haematological drug-related toxicity of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3. The MTD corresponded to the highest dose of volasertib and decitabine at which the incidence of DLT was ≤17% (i.e. 1/6 patients) during Cycle 1.
Number of Subjects With Dose Limiting Toxicities (DLT) in Cycle 1
Time frame: 4 weeks
Number of subjects with Dose Limiting Toxicities (DLT) in Cycle 1 is presented

Results and safety

Results posted to the registry on 31 Jan 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Volasertib 300 mg + Decitabine	3	0
Volasertib 350 mg + Decitabine	4	0
Volasertib 400 mg + Decitabine	6	0

Primary outcome: Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in Cycle 1

Time frame: 4 weeks. Number. Unit: Milligram (mg)

Measure	Volasertib + Decitabine n = 12
Value	400

Population analysed: TS. One patient treated with volasertib 350 mg + decitabine had to be excluded because they did not receive all planned doses of volasertib and could therefore not be included in the calculation of MTD. Thus overall 12 patients were analysed instead of 13 patients.

Primary outcome: Number of Subjects With Dose Limiting Toxicities (DLT) in Cycle 1

Time frame: 4 weeks. Number. Unit: participant

Measure	Volasertib 300 mg + Decitabine n = 3	Volasertib 350 mg + Decitabine n = 3	Volasertib 400 mg + Decitabine n = 6
Value	0	0	1

Population analysed: TS. One patient treated with volasertib 350 mg + decitabine had to be excluded because they did not receive all planned doses of volasertib and could therefore not be included in the calculation of MTD. Thus 3 patients were analysed instead of 4 patients for volasertib 350 mg + decitabine arm.

Adverse events

Time frame: All Adverse events with an onset after the first dose of study medication up to a period of 30 days after the last administration of study medication; up to 333 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Volasertib 300 mg + Decitabine	3 of 3 (100%)	3 of 3 (100%)	Not reported
Volasertib 350 mg + Decitabine	4 of 4 (100%)	4 of 4 (100%)	Not reported
Volasertib 400 mg + Decitabine	6 of 6 (100%)	6 of 6 (100%)	Not reported
Total	13 of 13 (100%)	13 of 13 (100%)	Not reported

Limitations and caveats (from the sponsor): This study was prematurely discontinued following the decision by the sponsor to discontinue the development of volasertib.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.

Related trials for Leukemia, Myeloid, Acute

RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing decitabine iv and volasertib iv infusion in people with Leukemia, Myeloid, Acute, run by Boehringer Ingelheim at 3 sites in United States.

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 7 inclusion and 20 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 31 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in Cycle 1 (time frame: 4 weeks). The study lists 2 primary outcomes in all. 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 NCT02003573.

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 31 Jan 2019.