Myelodysplastic SyndromesPhase 1NCT02721875
Trial of Volasertib With or Without Azacitidine in Patients With Myelodysplastic Syndromes
A Phase 1 study testing Volasertib and Azacitidine in people with Myelodysplastic Syndromes, run by Boehringer Ingelheim at 1 site in Japan.
Trial summary
The objectives of this trial are to evaluate the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics and preliminary efficacy of volasertib in two dosing schedules of intravenous volasertib as monotherapy or in combination with azacitidine in patients with myelodysplastic syndrome (MDS) after… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes
- What is being tested?
- Volasertib and Azacitidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteJapan
- Study dates
- 28 Apr 2016to 29 Jul 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
- Patients 18 years and older with diagnosis of WHO classification-defined primary or treatment-related myeloid neoplasms classified as follows:
- Refractory anaemia with excess blasts (RAEB)-1 (5%-9% marrow blasts) or
- RAEB-2 (10%-19% marrow blasts or 5% - 19% peripheral blast) or
- Chronic Myelomonocytic Leukaemia (CMML) (5%-19% blasts) with white blood cell (WBC) count <13000/mm3 or
- Acute Myeloid Leukaemia (AML) (20%-29% marrow blasts, i.e., RAEB-t according to French-American-British [FAB] classification) with WBC count <10000/mm3
- Patients classified as intermediate, high or very high-risk according to Revised - International Prognostic Scoring System (IPSS-R) at the time of enrolment
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- Patients who have received a maximum of 24 cycles of frontline HMA treatment prior to enrolment.
- Patients must have received a minimum prior dosing schedule of either:
- Azacitidine 75 mg/m2 x 5 days per cycle or 50 mg/m2 x 7 days per cycle, or
- Decitabine 20 mg/m2 x 5 days per cycle, or
- SGI-110 60 mg/m2 x 5 days per cycle
- Patients must meet either one of the following criteria:
- Progressive disease (PD, according to 2006 International Working Group (IWG) criteria) at any time after initiation of the prior HMA treatment, or
- Relapse after initial complete (CR) or partial remission (PR) or haematological improvement (HI) (according to 2006 IWG criteria); or
- Failure to achieve complete or partial remission or HI (according to 2006 IWG) with no evidence of progression (i.e., Stable Disease [SD]) after at least six cycles of prior azacitidine treatment or at least four cycles of other prior HMA treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 at screening
- Signed written informed consent consistent with International Conference of Harmonization Good Clinical Practice (ICH-GCP) and local legislation
Who cannot join
- Prior systemic therapy (including investigational drugs) for MDS, CMML or AML within 14 days before treatment with study medication.
- Patients requiring intervention for white blood cell count control with hydroxyurea, chemotherapy, or leukapheresis.
- Prior exposure to more than one line of HMA based treatment.
- Prior exposure to volasertib or other polo-kinase inhibitors
- Patients who were unable to tolerate prior HMA treatment
- Patients with history of hematopoietic stem cell transplant (HSCT)
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- Known hypersensitivity to the trial drugs or its excipients
- Second malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, e.g., in prostate or breast cancer).
- QTcF value >470 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open Label, Phase I Trial of Intravenous Administration of Volasertib as Monotherapy and in Combination With Azacitidine in Patients With Myelodysplastic Syndrome After Hypomethylating Agents Treatment Failure
The objectives of this trial are to evaluate the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics and preliminary efficacy of volasertib in two dosing schedules of intravenous volasertib as monotherapy or in combination with azacitidine in patients with myelodysplastic syndrome (MDS) after hypomethylating agents (HMA) treatment failure.
- Conditions
- Myelodysplastic Syndromes
- Being tested
- Volasertib, Azacitidine
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VolasertibDrug
VolasertibDrug
AzacitidineDrug
| Study group | Role | What they receive |
|---|---|---|
| Volasertib monotherapy | Experimental | Not described Receives: Drug: Volasertib |
| Volasertib + azacitidine combination | Experimental | Not described Receives: Drug: Volasertib; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Dose Limiting Toxicities (DLT) in the First Cycle
DLT was defined as any of the following adverse events (AEs) considered to be related to study drug: 1. Common terminology criteria for adverse events (CTCAE) v4.03 ≥Grade 3 drug related non- haematological toxicity, excluding; ≥Grade 3 untreated nausea, vomiting or diarrhea. Any laboratory abnormality - not considered clinically significant by investigator or resolved spontaneously or could have been recovered with appropriate treatment within 7 days. Grade 3 infection which could be recovered with appropriate treatment within 7 days. Azacitidine injection site reaction or complications related to azacitidine injection. 2. Febrile neutropenia as defined by CTCAE which could not recovered with appropriate treatment within 7 days. 3. Inability to deliver full dose of volasertib according to the assigned dose level within Cycle 1 due to drug-related AEs. 4. Haematological DLTs. 5. Any other drug-related AEs that resulted in the delay of starting new treatment cycle for ≥4 weeks.
Measured: First treatment cycle, up to 28 days
Maximum Tolerated Dose (MTD) of Volasertib
The MTD was defined as the highest dose with less than 35% risk of the true dose limiting toxicities (DLT) rate being above 0.33 for schedule A, and the highest dose with less than 40% risk of the true DLT rate being above 0.33 for schedule B. The phase I dose-finding was to be guided by a Bayesian 2-parameter logistic regression model (BLRM) with overdose control in each schedule separately.
Measured: First treatment cycle, up to 28 days
Secondary outcomes (5)
Objective Response Defined as Best Overall Response of Complete Remission, Partial Remission or Haematological Improvement According to the International Working Group 2006 Criteria
Objective response defined as best overall response of complete remission, partial remission or haematological improvement according to the International Working Group 2006 criteria. It is based on Complete remission (CR): Bone marrow: <=5% myeloblasts with normal maturation of all cell lines, Peripheral blood: Hemoglobin >=11 Grams Per Decilitre (g/dL), Platelets >=100 x 109/L, Neutrophils >=1.0 x 109/L, Blasts 0%. Peripheral blood responses had to last at least 4 weeks to qualify for CR. Partial remission (PR): All CR criteria if abnormal before treatment except: Bone marrow blasts decreased by >=50% to baseline but still >5%, Cellularity and morphology not relevant. Peripheral blood responses must last at least 4 weeks to qualify for PR. Haematological improvement (HI): HI was evaluated in patients with abnormal pretreatment values based on Erythroid response, Platelet response, Neutrophil response. Peripheral blood responses had to last at least 8 weeks to qualify for HI.
Measured: Up to 168 days
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Last Measured Time Point tz of Volasertib (AUC0-tz) (for Monotherapy)
Area under the plasma concentration-time curve over the time interval from zero to the last measured time point tz of volasertib (AUC0-tz) (for monotherapy).
Measured: Pharmacokinetic (PK) samples were taken at 5 minutes before drug administration and 0:30, 1:00, 2:00, 3:00, 4:00, 24:00, 167:55, 168:30, 169:00, 169:30, 170:00, 171:00, 172:00, 192:00, 336:00, 504:00, 672:00 hours after drug administration
Maximum Measured Plasma Concentration of Volasertib (Cmax) (for Monotherapy)
Maximum measured plasma concentration of volasertib (Cmax) (for monotherapy).
Measured: PK samples were taken at 5 minutes before drug administration and 0:30, 1:00, 2:00, 3:00, 4:00, 24:00, 167:55, 168:30, 169:00, 169:30, 170:00, 171:00, 172:00, 192:00, 336:00, 504:00, 672:00 hours after drug administration
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity of Volasertib (AUC0-∞) (for Combination)
Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity of volasertib (AUC0-∞) (for combination).
Measured: PK samples were to be taken at 5 minutes before drug administration (167:55) and 168:30, 169:00, 169:30, 170:00, 171:00, 172:00, 192:00, 336:00, 504:00, 672:00 hours after first drug administration of Azacitidine
Maximum Measured Plasma Concentration of Volasertib (Cmax) (for Combination)
Maximum measured plasma concentration of volasertib (Cmax) (for combination).
Measured: PK samples were to be taken at 5 minutes before drug administration (167:55) and 168:30, 169:00, 169:30, 170:00, 171:00, 172:00, 192:00, 336:00, 504:00, 672:00 hours after first drug administration of Azacitidine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2016 (estimated)
- Study start28 Apr 2016
- Primary completion29 Jun 2016
- Study completion29 Jul 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
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02721875
- Sponsor's protocol ID
- 1230.43
- Other IDs
- 2015-004490-32, 2015
- Status last verified
- Aug 2018
- First submitted
- 23 Mar 2016
- Last updated
- 9 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Phase I Trial of Intravenous Administration of Volasertib as Monotherapy and in Combination With Azacitidine in Patients With Myelodysplastic Syndrome After Hypomethylating Agents Treatment Failure
- ClinicalTrials.gov ID
- NCT02721875
- Acronym / sponsor ID
- 1230.43
- Conditions
- Myelodysplastic Syndromes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 28 Apr 2016 (actual)
- Primary completion
- 29 Jun 2016 (actual)
- Study completion
- 29 Jul 2016 (actual)
- First posted
- 29 Mar 2016 (estimated)
- Results
- Posted 9 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objectives of this trial are to evaluate the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics and preliminary efficacy of volasertib in two dosing schedules of intravenous volasertib as monotherapy or in combination with azacitidine in patients with myelodysplastic syndrome (MDS) after hypomethylating agents (HMA) treatment failure.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Volasertib monotherapy | Experimental | Drug: Volasertib |
| Volasertib + azacitidine combination | Experimental | Drug: Volasertib, Drug: Azacitidine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients 18 years and older with diagnosis of WHO classification-defined primary or treatment-related myeloid neoplasms classified as follows:
- Refractory anaemia with excess blasts (RAEB)-1 (5%-9% marrow blasts) or
- RAEB-2 (10%-19% marrow blasts or 5% - 19% peripheral blast) or
- Chronic Myelomonocytic Leukaemia (CMML) (5%-19% blasts) with white blood cell (WBC) count <13000/mm3 or
- Acute Myeloid Leukaemia (AML) (20%-29% marrow blasts, i.e., RAEB-t according to French-American-British [FAB] classification) with WBC count <10000/mm3
Key exclusion criteria (9 listed)
- Prior systemic therapy (including investigational drugs) for MDS, CMML or AML within 14 days before treatment with study medication.
- Patients requiring intervention for white blood cell count control with hydroxyurea, chemotherapy, or leukapheresis.
- Prior exposure to more than one line of HMA based treatment.
- Prior exposure to volasertib or other polo-kinase inhibitors
- Patients who were unable to tolerate prior HMA treatment
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 |
|---|---|---|
| Volasertib | Drug | Volasertib monotherapy |
| Volasertib | Drug | Volasertib + azacitidine combination |
| Azacitidine | Drug | Volasertib + azacitidine combination |
Primary outcome
Number of Patients With Dose Limiting Toxicities (DLT) in the First Cycle
Time frame: First treatment cycle, up to 28 days
DLT was defined as any of the following adverse events (AEs) considered to be related to study drug: 1. Common terminology criteria for adverse events (CTCAE) v4.03 ≥Grade 3 drug related non- haematological toxicity, excluding; ≥Grade 3 untreated nausea, vomiting or diarrhea. Any laboratory abnormality - not considered clinically significant by investigator or resolved spontaneously or could have been recovered with appropriate treatment within 7 days. Grade 3 infection which could be recovered with appropriate treatment within 7 days. Azacitidine injection site reaction or complications related to azacitidine injection. 2. Febrile neutropenia as defined by CTCAE which could not recovered with appropriate treatment within 7 days. 3. Inability to deliver full dose of volasertib according to the assigned dose level within Cycle 1 due to drug-related AEs. 4. Haematological DLTs. 5. Any other drug-related AEs that resulted in the delay of starting new treatment cycle for ≥4 weeks.
Maximum Tolerated Dose (MTD) of Volasertib
Time frame: First treatment cycle, up to 28 days
The MTD was defined as the highest dose with less than 35% risk of the true dose limiting toxicities (DLT) rate being above 0.33 for schedule A, and the highest dose with less than 40% risk of the true DLT rate being above 0.33 for schedule B. The phase I dose-finding was to be guided by a Bayesian 2-parameter logistic regression model (BLRM) with overdose control in each schedule separately.
5 secondary outcomes
Objective Response Defined as Best Overall Response of Complete Remission, Partial Remission or Haematological Improvement According to the International Working Group 2006 Criteria
Time frame: Up to 168 days
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Last Measured Time Point tz of Volasertib (AUC0-tz) (for Monotherapy)
Time frame: Pharmacokinetic (PK) samples were taken at 5 minutes before drug administration and 0:30, 1:00, 2:00, 3:00, 4:00, 24:00, 167:55, 168:30, 169:00, 169:30, 170:00, 171:00, 172:00, 192:00, 336:00, 504:00, 672:00 hours after drug administration
Maximum Measured Plasma Concentration of Volasertib (Cmax) (for Monotherapy)
Time frame: PK samples were taken at 5 minutes before drug administration and 0:30, 1:00, 2:00, 3:00, 4:00, 24:00, 167:55, 168:30, 169:00, 169:30, 170:00, 171:00, 172:00, 192:00, 336:00, 504:00, 672:00 hours after drug administration
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity of Volasertib (AUC0-∞) (for Combination)
Time frame: PK samples were to be taken at 5 minutes before drug administration (167:55) and 168:30, 169:00, 169:30, 170:00, 171:00, 172:00, 192:00, 336:00, 504:00, 672:00 hours after first drug administration of Azacitidine
Maximum Measured Plasma Concentration of Volasertib (Cmax) (for Combination)
Time frame: PK samples were to be taken at 5 minutes before drug administration (167:55) and 168:30, 169:00, 169:30, 170:00, 171:00, 172:00, 192:00, 336:00, 504:00, 672:00 hours after first drug administration of Azacitidine
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Volasertib and Azacitidine in people with Myelodysplastic Syndromes, run by Boehringer Ingelheim at 1 site 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 17 inclusion and 9 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 9 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 9 Aug 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 Patients With Dose Limiting Toxicities (DLT) in the First Cycle (time frame: First treatment cycle, up to 28 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?
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 9 Aug 2018.