Myelodysplastic SyndromesPhase 1NCT02201329

Volasertib in Combination With Azacitidine in Japanese Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

A Phase 1 study testing Azacitidine and Volasertib in people with Myelodysplastic Syndromes and Leukemia, Myelomonocytic, Chronic, run by Boehringer Ingelheim at 4 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

To identify the maximum tolerated dose or recommended dose for further development of volasertib in combination with azacitidine in Japanese patients with myelodysplastic syndromes or chronic myelomonocytic leukemia, and evaluate the safety and tolerability, pharmacokinetics and the preliminary efficacy of this… Read more about this study

Who is it for?: Ages 20 to 80 years
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: 5 participants
Where: 4 sitesJapan
Study dates: Aug 2014to Sep 2015
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 20 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients of age >=20 and <=80 years
Patients with primary or treatment-related myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), who are not eligible for hematopoietic stem cell transplantation based on the investigator's judgment, that meet one of the following criteria:
Intermediate-2 and high-risk MDS according to the International Prognostic Scoring System, in the setting of 5-30% bone marrow blasts
CMML with >= 10% marrow blasts without myeloproliferative disorder (white blood cell count of <13,000/ µL)
Patients with no prior azacitidine treatment, or with prior azacitidine treatment that meet one of the following criteria:
Patients failing to achieve haematological improvement, partial remission, marrow complete remission or complete remission after 3 cycles of azacitidine or progressed at any time after start of azacitidine

Show all 9Show fewer

Patients achieved an initial response and subsequently develop disease progression or relapse
Eastern Cooperative Oncology Group performance status score 0 or 1 at screening
Signed written informed consent consistent with Good Clinical Practice.

Who cannot join

Treatment with systemic therapy for MDS, including an investigational drug, within 14 days before the first dose of study treatment, except for lenalidomide within 12 weeks before the first dose of study treatment, or lack of recovery from any acute toxicities pertinent to the prior systemic therapy.
Prior treatment with volasertib
Contraindications for azacitidine treatment according to the manufacturer's product information
Known hypersensitivity to the trial drugs or its excipients
Concomitant malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer)
QTcF prolongation >470 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome).

Show all 17Show fewer

Total bilirubin >1.5 x upper limit of normal (ULN) not related to Gilbert's syndrome, hemolysis, or secondary to MDS at screening
Aspartate amino transferase or alanine amino transferase >2.5 x ULN
Serum creatinine >1.5 x ULN at screening
Arterial oxygen pressure <60 torr or arterial oxygen saturation <92% (at room air)
Active hepatitis B or hepatitis C, or laboratory evidence of hepatitis with positive results of hepatitis B surface antigen and/or hepatitis C antibody.
Human immunodeficiency virus infection.
Severe illness or organ dysfunction involving the heart, lung, kidney, liver or other organ system, which in the opinion of the investigator would interfere with the evaluation of the safety of the study treatment including; infection requiring active treatment, poorly controlled ventricular/atrial tachyarrhythmia, use of heart pacer, unstable angina pectoris, history of myocardial infarction or severe congestive heart failure, clinically unstable cardiac or pulmonary disease
Any 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
All male patients and female patients of child bearing potential who are unwilling to use a medically acceptable method of contraception during the trial and at least 6 months after the end of study treatment (i.e. hormonal contraception, intrauterine device, condom with spermicide, etc.). Note: females are considered to be of child bearing potential unless they have been surgically sterilized or are post-menopausal (complete absence of menses for at least 12 months without other medical reasons).
Pregnant or nursing female patients
Known or suspected active alcohol or drug abuse

Trial locations and contacts

4 sites in 1 country.

Japan4 sites

Boehringer Ingelheim Investigational Site
Aichi, Nagoya
Boehringer Ingelheim Investigational Site
Gunma, Maebashi
Boehringer Ingelheim Investigational Site
Nagasaki, Nagasaki
Boehringer Ingelheim Investigational Site
Tokyo, Sinagawa-ku

Other trials in Japan

About this study

Official title: An Open Label Phase I Trial of Intravenous Volasertib in Combination With Subcutaneous Azacitidine in Japanese Patients With Higher-risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

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
Azacitidine (subcutaneous)
VolasertibDrug
Volasertib escalating doses (intravenous)

Study groups in NCT02201329
Study group	Role	What they receive
A	Experimental	Volasertib escalating doses + azacitidine Receives: Drug: Azacitidine; Drug: Volasertib

What is being measured

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

Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)
This outcome measure presents number of participants with DLTs in the first cycle for the determination of MTD. DLT was defined as any of the following Adverse Events (AEs) considered to be related to the study drug (Volasertib and/or Azacitidine).
1. Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 drug-related non-haematologic toxicity.
2. Drug-related AEs that led to inability to deliver the full dose of the study drugs (Volasertib and/or Azacitidine) according to the assigned dose level within Cycle 1.
3. Absence of haematological recovery (sustained CTCAE grade ≥3 thrombocytopenia <50000/mm^3 and/or neutropenia <1000/mm^3) after completing Cycle 1 and lasting at least until Day 57 (from Day 1 of Cycle 1) despite complete marrow blast clearance on Day 29 (<5% blasts in the bone marrow.
4. Any other drug-related AEs that required treatment delay of ≥4 weeks between the Cycle 1 and Cycle 2 (i.e., Cycle 2 was not started until Day 57 of Cycle 1)).
Measured: Up to 57 days.
Maximum Tolerated Dose of Volasertib
This outcome measure presents MTD of Volasertib in Combination with Azacitidine. The MTD was defined as the highest dose level at which Dose Limiting Toxicities (DLTs) were reported in not more than 1 in 6 evaluable patients during Cycle 1.
Measured: Up to 57 days.

Secondary outcomes (3)

Overall Objective Response (OR): Complete Remission (CR), Partial Remission (PR), or Marrow CR (mCR)
This outcome measure presents overall Objective Response (CR+PR+mCR). Response to treatment was evaluated according to the International Working Group (IWG) 2006 criteria. Best response was tabulated from all available data, with each patient being classified into one of the categories defined in CR, PR, mCR.
Measured: Up to 9 months.
Maximum Measured Concentration of the Volasertib 200 mg in Plasma (Cmax)
This outcome measure presents maximum measured concentration of Volasertib 200 mg in plasma (Cmax).
Measured: -0.05 hours before drug administration and 0:30 (hours:minutes), 1:00, 1:30, 2:00, 3:00, 4:00, 24:30, 48:30, 96:30, 144:30 and 335:55 after drug administration.
Area Under the Concentration-Time Curve of Volasertib 200 mg in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
This outcome measure presents area under the concentration-time curve of Volasertib 200 mg + Azacitidine 75 mg/m^2 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).
Measured: -0.05 hours before drug administration and 0:30 (hours:minutes), 1:00, 1:30, 2:00, 3:00, 4:00, 24:30, 48:30, 96:30, 144:30 and 335:55 after drug administration.

Timeline

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

Aug 2014Sep 2015

First posted28 Jul 2014 (estimated)
Study startAug 2014
Primary completionJan 2015
Study completionSep 2015

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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02201329
Sponsor's protocol ID: 1230.35
Status last verified: Oct 2017
First submitted: 25 Jul 2014
Last updated: 30 Jul 2018
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

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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
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Myelodysplastic Syndromes
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Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
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All Myelodysplastic Syndromes trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open Label Phase I Trial of Intravenous Volasertib in Combination With Subcutaneous Azacitidine in Japanese Patients With Higher-risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
ClinicalTrials.gov ID: NCT02201329
Acronym / sponsor ID: 1230.35
Conditions: Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 5 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Aug 2014
Primary completion: Jan 2015 (actual)
Study completion: Sep 2015 (actual)
First posted: 28 Jul 2014 (estimated)
Results: Posted 30 Jul 2018

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: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
A	Experimental	Drug: Azacitidine, Drug: VolasertibVolasertib escalating doses + azacitidine

Who may qualify

Ages: 20 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Patients of age >=20 and <=80 years
Patients with primary or treatment-related myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), who are not eligible for hematopoietic stem cell transplantation based on the investigator's judgment, that meet one of the following criteria:
Patients with no prior azacitidine treatment, or with prior azacitidine treatment that meet one of the following criteria:
Eastern Cooperative Oncology Group performance status score 0 or 1 at screening
Signed written informed consent consistent with Good Clinical Practice.

Key exclusion criteria (17 listed)

Treatment with systemic therapy for MDS, including an investigational drug, within 14 days before the first dose of study treatment, except for lenalidomide within 12 weeks before the first dose of study treatment, or lack of recovery from any acute toxicities pertinent to the prior systemic therapy.
Prior treatment with volasertib
Contraindications for azacitidine treatment according to the manufacturer's product information
Known hypersensitivity to the trial drugs or its excipients
Concomitant malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer)

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
AzacitidineAzacitidine (subcutaneous)	Drug	A
VolasertibVolasertib escalating doses (intravenous)	Drug	A

Primary outcome

Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)
Time frame: Up to 57 days.
This outcome measure presents number of participants with DLTs in the first cycle for the determination of MTD. DLT was defined as any of the following Adverse Events (AEs) considered to be related to the study drug (Volasertib and/or Azacitidine). 1. Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 drug-related non-haematologic toxicity. 2. Drug-related AEs that led to inability to deliver the full dose of the study drugs (Volasertib and/or Azacitidine) according to the assigned dose level within Cycle 1. 3. Absence of haematological recovery (sustained CTCAE grade ≥3 thrombocytopenia <50000/mm^3 and/or neutropenia <1000/mm^3) after completing Cycle 1 and lasting at least until Day 57 (from Day 1 of Cycle 1) despite complete marrow blast clearance on Day 29 (<5% blasts in the bone marrow. 4. Any other drug-related AEs that required treatment delay of ≥4 weeks between the Cycle 1 and Cycle 2 (i.e., Cycle 2 was not started until Day 57 of Cycle 1)).
Maximum Tolerated Dose of Volasertib
Time frame: Up to 57 days.
This outcome measure presents MTD of Volasertib in Combination with Azacitidine. The MTD was defined as the highest dose level at which Dose Limiting Toxicities (DLTs) were reported in not more than 1 in 6 evaluable patients during Cycle 1.

3 secondary outcomes

Overall Objective Response (OR): Complete Remission (CR), Partial Remission (PR), or Marrow CR (mCR)
Time frame: Up to 9 months.
Maximum Measured Concentration of the Volasertib 200 mg in Plasma (Cmax)
Time frame: -0.05 hours before drug administration and 0:30 (hours:minutes), 1:00, 1:30, 2:00, 3:00, 4:00, 24:30, 48:30, 96:30, 144:30 and 335:55 after drug administration.
Area Under the Concentration-Time Curve of Volasertib 200 mg in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
Time frame: -0.05 hours before drug administration and 0:30 (hours:minutes), 1:00, 1:30, 2:00, 3:00, 4:00, 24:30, 48:30, 96:30, 144:30 and 335:55 after drug administration.

Results and safety

Results posted to the registry on 30 Jul 2018, 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 200 mg	5	0

Primary outcome: Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)

Time frame: Up to 57 days.. Number. Unit: Participants

Measure	Volasertib 200 mg n = 5
Value	2

Population analysed: MTD Set: This patient set included all patients in the treated set who were evaluable for MTD determination.

Primary outcome: Maximum Tolerated Dose of Volasertib

Time frame: Up to 57 days.. Number. Unit: mg

Measure	Volasertib 200 mg n = 5
Value	NA

Population analysed: MTD Set: This patient set included all patients in the treated set who were evaluable for MTD determination.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first drug administration until 30 days after last trial drug administration in the last treatment cycle or the decision of study treatment discontinuation, whichever is later, and was up to 389 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Volasertib 200 mg	2 of 5 (40%)	5 of 5 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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

4 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 Azacitidine and Volasertib in people with Myelodysplastic Syndromes and Leukemia, Myelomonocytic, Chronic, run by Boehringer Ingelheim at 4 sites in Japan.

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 9 inclusion and 17 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: finished, as of the sponsor's last update on 30 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Japan. 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 30 Jul 2018). 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?

Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD) (time frame: Up to 57 days.). 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 NCT02201329.

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 30 Jul 2018.