Myelodysplastic SyndromesPhase 1NCT01957644

Phase I Dose Escalation Trial of Volasertib in Combination With Azacitidine in Patients With MDS or CMML

A Phase 1 study testing Azacitidine and Volasertib in people with Myelodysplastic Syndromes and Leukemia, Myelomonocytic, Chronic, run by Boehringer Ingelheim at 14 sites in 2 countries.

Terminated

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

Official record

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Trial summary

To investigate the maximum tolerated dose (MTD), safety, pharmacokinetics, and efficacy of volasertib in combination with azacitidine in patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) and not candidates for hematopoietic stem cell transplant Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic
What is being tested?: Azacitidine and Volasertib
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 14 sitesin 2 countries
Study dates: 6 Nov 2013to 16 Dec 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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adult patients with previously untreated, intermediate-2 or high- risk MDS or CMML not eligible for hematopoietic stem cell transplantation (HSCT) based on documented patients characteristics like age, performance status, concomitant diagnoses, and organ dysfunctions
Further inclusion criteria apply

Who cannot join

Prior or concomitant therapy for higher risk MDS (for example, but not limited to, hypomethylating agents like azacitidine). Note: Prior treatment with erythropoetin (EPO) is allowed up to > 1 week before treatment with study medication. Patients must have not received MDS therapy since diagnosis of higher-risk MDS. However, previous lenalidomide treatment could have been administered for lower-risk MDS treatment as long as this therapy was discontinued at least > 4 weeks before initiation of the current study treatment.
Treatment with any investigational drug within 2 weeks before first administration of present trial drug or within less than 5 half lives of the investigational drug before treatment with the present trial drug, whichever is longer.
Second malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer).
Corrected QT interval according to Fridericia (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 the 3 Electrocardiograms (ECGs) taken at screening.
Total bilirubin > 1.5 x upper limit of normal not related to Gilberts disease, hemolysis, or secondary to MDS.
Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 2.5 x the upper limit of normal (ULN) Creatinine > 1.5 x ULN

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Active hepatitis B or hepatitis C, or laboratory evidence for a chronic infection (hepatitis test results done in routine diagnostics are acceptable if done within 14 days before first study treatment dose).
HIV infection (HIV test results in routine diagnostics are acceptable if done within 14 days before first study treatment dose).
Severe illness or organ dysfunction involving the kidney, liver or other organ system (e.g. active uncontrolled infection , unstable angina pectoris or history of severe congestive heart failure, clinically unstable cardiac disease or pulmonary disease), which in the opinion of the investigator would interfere with the evaluation of the safety of the study treatment
Further exclusion criteria apply

Trial locations and contacts

14 sites in 2 countries.

Country

City, postcode or hospital

14 sites in 2 countries

Germany12 sites

1230.33.49011 Boehringer Ingelheim Investigational Site
Berlin
1230.33.49002 Boehringer Ingelheim Investigational Site
Dresden
1230.33.49001 Boehringer Ingelheim Investigational Site
Düsseldorf
1230.33.49005 Boehringer Ingelheim Investigational Site
Frankfurt am Main
1230.33.49004 Boehringer Ingelheim Investigational Site
Freiburg im Breisgau
1230.33.49010 Boehringer Ingelheim Investigational Site
Hamburg
1230.33.49008 Boehringer Ingelheim Investigational Site
Hanover
1230.33.49012 Boehringer Ingelheim Investigational Site
Kassel
1230.33.49014 Boehringer Ingelheim Investigational Site
Leipzig
1230.33.49009 Boehringer Ingelheim Investigational Site
Mannheim
1230.33.49006 Boehringer Ingelheim Investigational Site
München
1230.33.49003 Boehringer Ingelheim Investigational Site
Ulm

Other trials in Germany

France2 sites

1230.33.33002 Boehringer Ingelheim Investigational Site
Marseille
1230.33.33001 Boehringer Ingelheim Investigational Site
Paris

Other trials in France

About this study

Official title: An Open Label Phase I Dose Escalation Trial to Investigate the Maximum Tolerated Dose, Safety, Pharmacokinetics and Efficacy of Intravenous Volasertib in Combination With Subcutaneous Azacitidine in Patients With Previously Untreated High-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) and Not Candidates for Haematopoetic Stem Cell Transplant

Conditions: Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic
Being tested: Azacitidine, Volasertib
Medical subject headings: Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic

What participants receive

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

AzacitidineDrug
VolasertibDrug

Study groups in NCT01957644
Study group	Role	What they receive
Schedule A	Experimental	Volasertib (d1 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle) Receives: Drug: Azacitidine; Drug: Volasertib
Schedule B	Experimental	Volasertib (d 7 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle) Receives: Drug: Azacitidine; Drug: Volasertib
Schedule C	Experimental	Volasertib (d 1 and 7 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle) Receives: Drug: Azacitidine; Drug: Volasertib

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 azacitidine. 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 azacitidine at which the incidence of DLT was ≤17% (i.e. 1/6 patients) during Cycle 1.
The planned dose escalation schedules of Part 2 were not completed because the trial was prematurely discontinued. Hence, a final conclusion of the MTD of volasertib in combination with azacitidine cannot be drawn in this trial.
Number of patients with DLT in cycle 1 in escalation part is presented to determine MTD.
Measured: 4 weeks
Number of Participants With Dose Limiting Toxicities (DLT) in Cycle 1
Number of participants with Dose Limiting Toxicities (DLT) in Cycle 1 (escalation part to determine MTD) is presented .
Measured: 4 weeks

Secondary outcomes (1)

Percentage of Patients With Objective Response (OR)
OR was defined as best overall response of complete remission (CR) or partial remission (PR) defined according to the International Working Group (IWG) 2006 criteria.
Complete remission (CR):
- Bone marrow: <5 % myeloblasts with normal maturation of all cell lines*
- Persistent dysplasia will be noted*
- Peripheral blood:
- hemoglobin (Hgb) > 11 Grams Per Decilitre (g/dL)
- Platelets >100 x 109/L
- Neutrophils > 1.0 x 109/L
- Blasts 0 % *Dysplastic changes should consider the normal range of dysplastic changes
Partial remission (PR):
All CR criteria if abnormal before treatment except:
- Bone marrow blasts decreased by >50% to pre-treatment but still >5%
- Cellularity and morphology not relevant
Measured: From randomisation until data cut-off (16Dec2016); up to 159 weeks

Timeline

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

6 Nov 201316 Dec 2016

First posted8 Oct 2013 (estimated)
Study start6 Nov 2013
Primary completion16 Dec 2016
Study completion16 Dec 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 Myelodysplastic SyndromesStudies 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
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01957644
Sponsor's protocol ID: 1230.33
Other IDs: 2013-001290-24
Status last verified: Sep 2018
First submitted: 1 Oct 2013
Last updated: 8 Feb 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 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 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
High Grade Myelodysplastic Syndromes
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
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
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 Myelodysplastic Syndromes trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Feb 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 Intravenous Volasertib in Combination With Subcutaneous Azacitidine in Patients With Previously Untreated High-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) and Not Candidates for Haematopoetic Stem Cell Transplant
ClinicalTrials.gov ID: NCT01957644
Acronym / sponsor ID: 1230.33
Conditions: Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic
Phase: Phase 1
Study type: Interventional
Recruitment status: Terminated
Enrolment: 16 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 6 Nov 2013 (actual)
Primary completion: 16 Dec 2016 (actual)
Study completion: 16 Dec 2016 (actual)
First posted: 8 Oct 2013 (estimated)
Results: Posted 8 Feb 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
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Schedule A	Experimental	Drug: Azacitidine, Drug: VolasertibVolasertib (d1 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)
Schedule B	Experimental	Drug: Azacitidine, Drug: VolasertibVolasertib (d 7 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)
Schedule C	Experimental	Drug: Azacitidine, Drug: VolasertibVolasertib (d 1 and 7 - one hour iv.) + Azacitidine 75 mg/m2 once daily on Days 1-7 (7 consecutive days) (28-day cycle)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Adult patients with previously untreated, intermediate-2 or high- risk MDS or CMML not eligible for hematopoietic stem cell transplantation (HSCT) based on documented patients characteristics like age, performance status, concomitant diagnoses, and organ dysfunctions
Further inclusion criteria apply

Key exclusion criteria (10 listed)

Prior or concomitant therapy for higher risk MDS (for example, but not limited to, hypomethylating agents like azacitidine). Note: Prior treatment with erythropoetin (EPO) is allowed up to > 1 week before treatment with study medication. Patients must have not received MDS therapy since diagnosis of higher-risk MDS. However, previous lenalidomide treatment could have been administered for lower-risk MDS treatment as long as this therapy was discontinued at least > 4 weeks before initiation of the current study treatment.
Treatment with any investigational drug within 2 weeks before first administration of present trial drug or within less than 5 half lives of the investigational drug before treatment with the present trial drug, whichever is longer.
Second malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer).
Corrected QT interval according to Fridericia (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 the 3 Electrocardiograms (ECGs) taken at screening.
Total bilirubin > 1.5 x upper limit of normal not related to Gilberts disease, hemolysis, or secondary to MDS.

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
Azacitidine	Drug	Schedule A, Schedule B, Schedule C
Volasertib	Drug	Schedule A, Schedule B, Schedule C

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 azacitidine. 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 azacitidine at which the incidence of DLT was ≤17% (i.e. 1/6 patients) during Cycle 1. The planned dose escalation schedules of Part 2 were not completed because the trial was prematurely discontinued. Hence, a final conclusion of the MTD of volasertib in combination with azacitidine cannot be drawn in this trial. Number of patients with DLT in cycle 1 in escalation part is presented to determine MTD.
Number of Participants With Dose Limiting Toxicities (DLT) in Cycle 1
Time frame: 4 weeks
Number of participants with Dose Limiting Toxicities (DLT) in Cycle 1 (escalation part to determine MTD) is presented .

1 secondary outcome

Percentage of Patients With Objective Response (OR)
Time frame: From randomisation until data cut-off (16Dec2016); up to 159 weeks

Results and safety

Results posted to the registry on 8 Feb 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 250 mg + Azacitidine (Escalation Cohort)-Part 1	6	0
Volasertib 300 mg + Azacitidine (Escalation Cohort)- Part 1	6	0
Volasertib 250 mg + Azacitidine (Expansion Cohort)- Part 1	1	0
Volasertib 170 mg/m2 + Azacitidine (Escalation Cohort)- Part 2	2	0
Volasertib 110 mg/m2 + Azacitidine (Escalation Cohort)- Part 2	1	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 250 mg + Azacitidine (Escalation Cohort)-Part 1 n = 6	Volasertib 300 mg + Azacitidine (Escalation Cohort)- Part 1 n = 5	Volasertib 170 mg/m2 + Azacitidine (Escalation Cohort)- Part 2 n = 1	Volasertib 110 mg/m2 + Azacitidine (Escalation Cohort)- Part 2 n = 1
Value	NA	NA	NA	NA

Population analysed: MTD set: The MTD set was used for the first treatment cycle (Cycle 1) analysis and excluded any treated patients that missed any dose of trial medication in Cycle 1 for reasons other than DLT

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

Time frame: 4 weeks. Number. Unit: participants

Measure	Volasertib 250 mg + Azacitidine (Escalation Cohort)-Part 1 n = 6	Volasertib 300 mg + Azacitidine (Escalation Cohort)- Part 1 n = 5	Volasertib 170 mg/m2 + Azacitidine (Escalation Cohort)- Part 2 n = 1	Volasertib 110 mg/m2 + Azacitidine (Escalation Cohort)- Part 2 n = 1
Value	1	1	0	1

Population analysed: MTD set

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From randomisation until data cut-off (16Dec2016); up to 159 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Volasertib 250 mg + Azacitidine (Escalation Cohort)-Part 1	6 of 6 (100%)	6 of 6 (100%)	Not reported
Volasertib 300 mg + Azacitidine (Escalation Cohort)- Part 1	2 of 6 (33.3%)	5 of 6 (83.3%)	Not reported
Volasertib 250 mg + Azacitidine (Expansion Cohort)- Part 1	0 of 1 (0%)	1 of 1 (100%)	Not reported
Volasertib 170 mg/m2 + Azacitidine (Escalation Cohort)- Part 2	0 of 2 (0%)	2 of 2 (100%)	Not reported
Volasertib 110 mg/m2 + Azacitidine (Escalation Cohort)- Part 2	1 of 1 (100%)	1 of 1 (100%)	Not reported

Limitations and caveats (from the sponsor): The sponsor discontinued the development of volasertib on 25 Nov 2016 and this trial was discontinued on 16 Dec 2016 for non-clinical reasons. The number of patients enrolled in Part 2 of the study was too small for a meaningful analysis.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.

Related trials for Myelodysplastic Syndromes

RecruitingPhase 2
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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

14 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Azacitidine and Volasertib in people with Myelodysplastic Syndromes and Leukemia, Myelomonocytic, Chronic, run by Boehringer Ingelheim at 14 sites in 2 countries.

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 2 inclusion and 10 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 8 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Germany, France. 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 8 Feb 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 NCT01957644.

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 8 Feb 2019.