LeukemiaPhase 1NCT01971476
Open Dose Escalating Trial to Determine the Maximum Tolerated Dose in Paediatric Patients With Advanced Cancers for Whom no Therapy is Known
A Phase 1 study testing volasertib in people with Leukemia and Neoplasms, run by Boehringer Ingelheim at 5 sites in 5 countries.
Trial summary
The present trial will be performed according to an open design to determine the maximum tolerable dose (MTD) by evaluation of dose-limiting toxicity (DLT) of volasertib in paediatric leukaemia and solid tumours in the age group 2 to less than 12 and 12 to less than 18 years. Read more about this study
- Who is it for?
- Ages 2 to 17 years
- What is being tested?
- volasertib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 5 sitesin 5 countries
- Study dates
- 22 Oct 2013to 27 Jan 2017
- 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 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- paediatric patients with leukaemia or advanced solid tumours including lymphomas (age 2 - less than 18 years) for whom no further treatment is known
- Lansky score > 60 for children 2 to less than 12 years
- Karnofsky score > 60 for children aged 12 or older
- life expectancy of at least 6 weeks as judged by the investigator
- parents or legal guardians have given written informed consent and informed assent suitable for the respective age group obtained
Who cannot join
- patient eligible for other anti-leukaemic therapy with curative intent or effective therapy known for solid tumour therapy
- presence of cardiac disease (LVEF by echocardiography less than 25 %)
- symptomatic Central Nervous System involvement of the malignant disease
- primary CNS tumour
- inadequate lab parameters
- inadequate venous access
Show all 9Show fewer
- QTc prolongation
- pregnancy, breastfeeding
- other diseases or CTs that might interfere with evaluation of safety
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
About this study
Official title: Open, Non-controlled, Dose Escalating Phase I Trial to Evaluate the Pharmacokinetics, Pharmacodynamics, Tolerability and Toxicity of Volasertib in Paediatric Patients From 2 Years to Less Than 18 Years of Age With Acute Leukaemia or Advanced Solid Tumour, for Whom no Effective Treatment is Known
The present trial will be performed according to an open design to determine the maximum tolerable dose (MTD) by evaluation of dose-limiting toxicity (DLT) of volasertib in paediatric leukaemia and solid tumours in the age group 2 to less than 12 and 12 to less than 18 years. A further objective is to collect data on safety, tolerability, toxicity, efficacy (preliminary activity), pharmacokinetics and pharmacodynamics of volasertib in paediatric cancer patients
- Being tested
- volasertib
- Medical subject headings
- Leukemia, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
volasertibDrug
intravenous administration on day 1of a treatment course
| Study group | Role | What they receive |
|---|---|---|
| All patients | Experimental | Volasertib will be administered as intravenous infusion Receives: 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. DLTs were defined as drug related Common Terminology Criteria for Adverse Events (CTCAE) ≥Grade 3 (haematological and nonhaematological) Adverse Events (AEs) with the exception of a) Reduced blood cell count (any grade) without associated clinical complications qualifying for DLT. b) Febrile neutropenia Grade 3. c) Infection Grade 3 with neutrophil count <1000/mm3. d) Uric acid Grade ≥3. e) Nausea, vomiting and/or diarrhoea managed by adequate therapy (i.e. recovery to CTCAE Grade ≤2).
Measured: Up to 14 days.
Maximum Tolerated Dose of Volasertib
This outcome measure presents MTD of Volasertib. The MTD was defined as the highest dose level at which DLTs were reported in not more than 1 in 6 evaluable patients during Cycle 1.
Measured: Up to 14 days.
Secondary outcomes (10)
Number of Patients With Hepatic Injury Defined as Adverse Events of Special Interest (AESI)
This outcome measure presents number of patients with hepatic injury defined as AESI. Hepatic injury was defined by the following alterations of liver parameters: an elevation of Aspartate Transaminase (AST) and/or Alanine Transaminase (ALT) >3x Upper Limit of Normal (ULN) combined with an elevation of total bilirubin >2x ULN measured in the same blood sample.
Measured: Up to 879 days.
Number of Patients With Clinically Relevant Laboratory Value Changes of Calcium (Hyper- and/or Hypocalcaemia) as Judged by the Investigator and Reported as AEs, CTCAE Grade ≥3
This outcome measure presents number of patients with clinically relevant laboratory value changes of calcium (hyper- and/or hypocalcaemia) as judged by the investigator and reported as AEs, CTCAE Grade ≥3. CTCAE Grade 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Measured: Up to 879 days.
The Number of Patients With Changes in Cardiac Activity (Prolonged QTc Interval) Reported as Clinically Relevant Observations
This outcome measure presents the number of patients with changes in cardiac activity (prolonged QTc interval) reported as clinically relevant observations to assess cardiac activity based on Electrocardiogram (ECG) recordings (digital, triplicate) before and at the end of each Volasertib administration and at least at 2 more time points within the first 24 hours after end of the first Volasertib administration. Two methods of heart rate correction of the QT interval were used: the fixed corrections Fridericia's correction (QTcF) and Bazett's correction (QTcB).
SMQ: Standardised Medical Dictionary for Regulatory Activities (MedDRA) query.
Measured: Up to 879 days.
Best Overall Response [in Leukaemia Patients]: (Complete Remission (CR)), CR With Incomplete Neutrophil or Platelet Recovery (CRi), Partial Remission (PR), Stable Disease (SD), Progressive Disease (PD) and Death in Aplasia
This outcome measure includes, CR: Bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary (EM) disease; absolute neutrophil count ≥ 1.0 x 109/L (1000/μL); platelet count ≥80 x 109/L (80000/μL); independence of red blood cells transfusions. CRi: All CR criteria except for residual neutropenia (<1.0 x 109/L [1000/μL]) or thrombocytopenia (<800 x 109/L [80000/μL]), independence of red blood cell transfusions not required. PR: Decrease of bone marrow blast percentage to 5%-25%; decrease of pretreatment bone marrow (baseline) blast percentage by at least 50%; absence of EM disease. SD: Neither qualifies for CR, CRi, PR or PD. PD: At least one of the criteria a) 50% increase in bone marrow blast count over baseline b) 50% increase in peripheral blast count over baseline - evidence of new EM disease - clinically PD based on the judgment of the investigator. Death in aplasia: Deaths occurring ≥7 days after last administration of the trial drug while cytopenic.
Measured: Up to 849 days.
Event-Free Survival (EFS) [in Leukaemia Patients]
EFS was defined as the time from the first infusion of Volasertib to the date of PD or relapse, occurrence of secondary malignancy, or death from any cause, whichever occurred first. EFS was censored at the date of last disease assessment for patients who were not reported with PD, relapse, occurrence of secondary malignancy or death.
Measured: Up to 849 days.
Overall Survival (OS) [in Leukaemia Patients]
Overall survival was defined as time from first infusion of Volasertib to death from any cause. For patients who were lost to follow-up, OS were censored on the last date the patients were known to be alive.
Measured: Up to 849 days.
Maximum Measured Concentration (Cmax, Norm) of Volasertib
This outcome measure presents dose normalized maximum measured concentration of Volasertib in plasma (Cmax, norm).
Measured: Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
Trough Concentration (Cpre, 2) of Volasertib
This outcome measure presents pre-dose concentration of Volasertib in plasma immediately before administration of the second dose (Cpre,2).
The number of participants analysed displays the number of participants with available data at the timepoint of interest.
Measured: Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
Area Under the Concentration-Time Curve (AUC0-∞, Norm) of Volasertib in Plasma
This outcome measure presents dose normalized area under the concentration-time curve of Volasertib in plasma over the time interval from zero extrapolated to infinity.
Measured: Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
Half-Life (t1/2) of Volasertib
This outcome measure presents half-life of Volasertib.
Measured: Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2013 (estimated)
- Study start22 Oct 2013
- Primary completion1 Jun 2015
- Study completion27 Jan 2017
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 LeukemiaStudies 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
- 22 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
- NCT01971476
- Sponsor's protocol ID
- 1230.27
- Other IDs
- 2013-001291-38
- Status last verified
- Oct 2017
- First submitted
- 10 Oct 2013
- Last updated
- 30 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
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
- Open, Non-controlled, Dose Escalating Phase I Trial to Evaluate the Pharmacokinetics, Pharmacodynamics, Tolerability and Toxicity of Volasertib in Paediatric Patients From 2 Years to Less Than 18 Years of Age With Acute Leukaemia or Advanced Solid Tumour, for Whom no Effective Treatment is Known
- ClinicalTrials.gov ID
- NCT01971476
- Acronym / sponsor ID
- 1230.27
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 22 Oct 2013 (actual)
- Primary completion
- 1 Jun 2015 (actual)
- Study completion
- 27 Jan 2017 (actual)
- First posted
- 29 Oct 2013 (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.
The present trial will be performed according to an open design to determine the maximum tolerable dose (MTD) by evaluation of dose-limiting toxicity (DLT) of volasertib in paediatric leukaemia and solid tumours in the age group 2 to less than 12 and 12 to less than 18 years. A further objective is to collect data on safety, tolerability, toxicity, efficacy (preliminary activity), pharmacokinetics and pharmacodynamics of volasertib in paediatric cancer patients
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All patients | Experimental | Drug: volasertibVolasertib will be administered as intravenous infusion |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- paediatric patients with leukaemia or advanced solid tumours including lymphomas (age 2 - less than 18 years) for whom no further treatment is known
- Lansky score > 60 for children 2 to less than 12 years
- Karnofsky score > 60 for children aged 12 or older
- life expectancy of at least 6 weeks as judged by the investigator
- parents or legal guardians have given written informed consent and informed assent suitable for the respective age group obtained
Key exclusion criteria (9 listed)
- patient eligible for other anti-leukaemic therapy with curative intent or effective therapy known for solid tumour therapy
- presence of cardiac disease (LVEF by echocardiography less than 25 %)
- symptomatic Central Nervous System involvement of the malignant disease
- primary CNS tumour
- inadequate lab parameters
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 |
|---|---|---|
| volasertibintravenous administration on day 1of a treatment course | Drug | All patients |
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 14 days.
This outcome measure presents number of participants with DLTs in the first cycle for the determination of MTD. DLTs were defined as drug related Common Terminology Criteria for Adverse Events (CTCAE) ≥Grade 3 (haematological and nonhaematological) Adverse Events (AEs) with the exception of a) Reduced blood cell count (any grade) without associated clinical complications qualifying for DLT. b) Febrile neutropenia Grade 3. c) Infection Grade 3 with neutrophil count <1000/mm3. d) Uric acid Grade ≥3. e) Nausea, vomiting and/or diarrhoea managed by adequate therapy (i.e. recovery to CTCAE Grade ≤2).
Maximum Tolerated Dose of Volasertib
Time frame: Up to 14 days.
This outcome measure presents MTD of Volasertib. The MTD was defined as the highest dose level at which DLTs were reported in not more than 1 in 6 evaluable patients during Cycle 1.
10 secondary outcomes
Number of Patients With Hepatic Injury Defined as Adverse Events of Special Interest (AESI)
Time frame: Up to 879 days.
Number of Patients With Clinically Relevant Laboratory Value Changes of Calcium (Hyper- and/or Hypocalcaemia) as Judged by the Investigator and Reported as AEs, CTCAE Grade ≥3
Time frame: Up to 879 days.
The Number of Patients With Changes in Cardiac Activity (Prolonged QTc Interval) Reported as Clinically Relevant Observations
Time frame: Up to 879 days.
Best Overall Response [in Leukaemia Patients]: (Complete Remission (CR)), CR With Incomplete Neutrophil or Platelet Recovery (CRi), Partial Remission (PR), Stable Disease (SD), Progressive Disease (PD) and Death in Aplasia
Time frame: Up to 849 days.
Event-Free Survival (EFS) [in Leukaemia Patients]
Time frame: Up to 849 days.
Overall Survival (OS) [in Leukaemia Patients]
Time frame: Up to 849 days.
Maximum Measured Concentration (Cmax, Norm) of Volasertib
Time frame: Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
Trough Concentration (Cpre, 2) of Volasertib
Time frame: Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
Area Under the Concentration-Time Curve (AUC0-∞, Norm) of Volasertib in Plasma
Time frame: Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
Half-Life (t1/2) of Volasertib
Time frame: Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
Results and safety
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.
Related trials for Leukemia
RecruitingPhase 3
Pivotal Open-label Phase 3 Clinical Study of QTX-2101 in Adult Patients With Acute Promyelocytic Leukemia
Acute Promyelocytic Leukemia (APL), Acute Promyelocytic Leukaemia
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Active, not recruitingPhase 1/2
Study to Evaluate the Safety and Preliminary Efficacy of Ibrutinib and Pembrolizumab in Patients With Chronic Lymphocytic Leukemia (CLL) or Mantle Cell Lymphoma (MCL)
Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma
RecruitingPhase 1
Anti-CRLF2-R/TSLPR Chimeric Antigen Receptor T Cells (TSLPR-CART) in Participants With Recurrent or Refractory CRLF2-R/TSLPR-Overexpressing B-Cell Acute Lymphoblastic Leukemia (B-ALL)
B-All, Acute Lymphoblastic Leukemia
Active, not recruiting
High-Intensity Parent Intervention Program in Improving Learning and School Functioning in Latino Children With Acute Leukemia or Lymphoblastic Lymphoma
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
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
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing volasertib in people with Leukemia and Neoplasms, run by Boehringer Ingelheim at 5 sites in 5 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 5 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: 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 5 sites in Belgium, Czechia, France, Germany, Italy. 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 14 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 30 Jul 2018.