Leukemia, Myeloid, AcutePhase 1VIACNCT02527174
A Study of Volasertib Plus Induction Chemotherapy for Acute Myeloid Leukemia
A Phase 1 study testing Volasertib, Idarubicin and Cytarabine in people with Leukemia, Myeloid, Acute and Leukemia, Monocytic, Acute, run by University of Alberta at 2 sites in Canada.
Trial summary
This is a Phase I clinical trial to determine the maximum tolerated dose (MTD) of the polo-like kinase-1 inhibitor volasertib which can be safely combined with idarubicin plus cytarabine induction chemotherapy for previously untreated patients with acute myeloid leukemia. (AML). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Leukemia, Myeloid, Acute, Leukemia, Monocytic, Acute, Leukemia, Myelomonocytic, Acute
- What is being tested?
- Volasertib, Idarubicin and Cytarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesCanada
- Study dates
- Nov 2016to Sep 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- AML, any World Health Organization (WHO) subtype except APL, either de novo or secondary; extramedullary AML (i.e. granulocytic sarcoma) is permitted.
- At least one of the following features:
- Age 18-75 with adverse risk cytogenetics, including:
- Complete or partial deletion of chromosome 5 or 7
- Complex karyotype, defined as > 3 abnormalities, excluding t(15;17). t(8;21) or inv(16) or variant
- 11q23 abnormality
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- Inv(3)(q21;q26) or variant
- t(6;9)
- abn(17p)
- Age 18-75 with secondary AML, defined as arising from an antecedent myelodysplastic syndrome (MDS) or myeloproliferative disorder (MPD), or therapy-related AML
- Age 60-75, regardless of risk category
- No prior therapy for AML other than hydroxyurea (allowed for up to 28 days). Prior therapy for MDS, MPD or other malignancy is allowed.
- Judged by treating physician to be medically fit for induction chemotherapy
- ECOG performance status score 0-2.
- Left ventricular ejection fraction (LVEF) within normal limits, by myocardial multigated scan (MUGA) or echocardiogram.
- Signed and dated written informed consent prior to admission
Who cannot join
- Prior anthracycline exposure equivalent to > 300 mg/m2 doxorubicin.
- Prior chemotherapy or radiotherapy within previous four weeks except for hydroxyurea.
- Prior treatment with volasertib or any other Polo-like kinase inhibitor
- Known hypersensitivity to the trial drug
- Serum creatinine > 1.5 times (1.5x) upper limit of normal (ULN) or creatinine clearance (CLcr) < 30 ml/min (estimated creatinine clearance by the Cockcroft-Gault (C-G) equation
- Serum bilirubin > 1.5x ULN, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3x ULN
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- Persistence of clinically relevant therapy related toxicity from previous anti-cancer therapy
- Active central nervous system leukemia (no lumbar puncture required; clinical judgement is sufficient)
- Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial
- Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure (> New York Heart Association-II), serious cardiac arrhythmia, pericardial effusion)
- 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 ECGs taken at screening.
- Other concurrent malignancy requiring active therapy (except hormonal therapy for prostate or breast cancer).
- Severe uncontrolled infection. Controlled infection on antibiotics is permitted.
- Active or chronic hepatitis C and/or B infection
- Known HIV infection
- Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study.
- Patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial and for at least six months after end of active therapy on study.
- Pregnancy or breast feeding, female patients must have a negative pregnancy test prior to commencing study treatment.
- Psychological, familial or sociological factors potentially hampering compliance with the study protocol and follow-up schedule
- Known or suspected active alcohol or drug abuse
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2
University of Alberta Hospital
Edmonton, Alberta, T6G 2G3
About this study
Official title: A Phase I Study of Volasertib Combined With Standard Induction Chemotherapy for Previously Untreated Patients With Acute Myeloid Leukemia (VIAC)
This is a Phase I clinical trial to determine the maximum tolerated dose (MTD) of the polo-like kinase-1 inhibitor volasertib which can be safely combined with idarubicin plus cytarabine induction chemotherapy for previously untreated patients with acute myeloid leukemia. (AML).
Read the detailed description
Main inclusion criteria:
- AML, any subtype except acute promyelocytic leukemia (APL)
- At least one of the following features:
- Age 18-75 with adverse risk cytogenetics ii. Age 18-75 with antecedent myelodysplastic syndrome (MDS) or myeloproliferative disorder (MPD), or therapy-related AML iii. Age 60-75, regardless of risk category
- No prior therapy for AML other than hydroxyurea
- Judged by treating physician to be medically fit for induction chemotherapy
- Eastern Cooperative Oncology Group (ECOG) performance status score 0-2
- Normal left ventricular ejection fraction
Subjects will receive induction chemotherapy consisting of idarubicin 12 mg/m2 on Days 1-3 plus cytarabine 200 mg/m2 (age 18-59) or 100 mg/m2 (age 60-75) as a continuous IV infusion x 7 days. Volasertib will be administered on day 4 in a dose-escalation schedule, using a standard 3+3 dose escalation design, over 3 dose levels. Once the MTD has been determined, an additional dose expansion cohort will be accrued.
- Conditions
- Leukemia, Myeloid, Acute, Leukemia, Monocytic, Acute, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute, Leukemia, Megakaryoblastic, Acute
- Being tested
- Volasertib, Idarubicin, Cytarabine
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Monocytic, Acute, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute, Leukemia, Megakaryoblastic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VolasertibDrug
Also called BI 6727
Addition of single dose of volasertib intravenously (IV) on Day 4 of treatment protocol.
IdarubicinDrug
Given IV daily on Days 1-3 of treatment protocol.
CytarabineDrug
Also called Ara-C
Given IV daily as 24-hour continuous infusion on Day 1-7 of treatment protocol.
| Study group | Role | What they receive |
|---|---|---|
| Study treatment arm | Experimental | Will receive volasertib combined with idarubicin plus cytarabine in a 3+7 schedule as induction chemotherapy. Volasertib dose will be given on day 4 in a dose escalation schedule over 3 dose levels (140 mg/m2, 170 mg/m2, 200 mg/m2) in successive cohorts.
Non-hematologic toxicity will be determined using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria for adverse events. Hematologic toxicity will be determined by days to absolute neutrophil count (ANC) and platelet recovery. Receives: Drug: Volasertib; Drug: Idarubicin; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity profile
Non-hematologic toxicities will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Hematologic toxicities will be assessed by determining number of days to neutrophil (ANC) recovery to >0.5 x10(9)/L or platelet recovery to >20 x10(9)/L.
Measured: Participants will be followed for duration of induction cycle (expected time 28-35 days) for toxicity.
Dose-limiting toxicity (DLT)
DLT is defined as grade 3-4 non-hematologic toxicity (except grade 3 nausea, vomiting, mucositis or creatinine elevation due to tumor lysis syndrome, and grade 3-4 neutropenic infections and electrolyte abnormalities) using CTCAE version 4.0.Hematologic DLT is defined as ANC recovery to >0.5 x10(9)/L or platelet recovery to >20 x10(9)/L of > 42 days.
Measured: Participants will be followed for duration of induction cycle (expected time 28-35 days) for DLT assessment.
Maximum tolerated dose (MTD)
MTD is defined as maximum dose of volasertib associated with < 2/6 DLTs at a given dose level.
Measured: Determined after completion of dose-escalation phase of study, which will take approx. 12-15 months.
Secondary outcomes (1)
Complete response rate of regimen
Complete response (CR) defined as <5% marrow blasts with ANC > 1.0 x10(9)/L and platelets >100 x 10(9)/L, with no extramedullary disease. CRi defined as same, but ANC <1.0 and/or platelets <100.
Measured: Responses will be determined at hematologic recovery (Day 28 or greater, up to Day 60).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2015 (estimated)
- Study startNov 2016
- Primary completionMay 2018 (estimated)
- Study completionSep 2018 (estimated)
Why it stopped: Volasertib no longer available
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joseph Brandwein, University of Alberta
- Investigators
- Joseph Brandwein, MD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02527174
- Sponsor's protocol ID
- 1230-37
- Acronym
- VIAC
- Status last verified
- Apr 2017
- First submitted
- 6 Jul 2015
- Last updated
- 5 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Anonymized data will be made available to Boehringer-Ingelheim.
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Volasertib Combined With Standard Induction Chemotherapy for Previously Untreated Patients With Acute Myeloid Leukemia (VIAC)
- ClinicalTrials.gov ID
- NCT02527174
- Acronym / sponsor ID
- VIAC / 1230-37
- Conditions
- Leukemia, Myeloid, Acute, Leukemia, Monocytic, Acute, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute, Leukemia, Megakaryoblastic, Acute
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Volasertib no longer available
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Study start
- Nov 2016
- Primary completion
- May 2018 (estimated)
- Study completion
- Sep 2018 (estimated)
- First posted
- 18 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I clinical trial to determine the maximum tolerated dose (MTD) of the polo-like kinase-1 inhibitor volasertib which can be safely combined with idarubicin plus cytarabine induction chemotherapy for previously untreated patients with acute myeloid leukemia. (AML).
Detailed description
Main inclusion criteria:
- AML, any subtype except acute promyelocytic leukemia (APL)
- At least one of the following features:
- Age 18-75 with adverse risk cytogenetics ii. Age 18-75 with antecedent myelodysplastic syndrome (MDS) or myeloproliferative disorder (MPD), or therapy-related AML iii. Age 60-75, regardless of risk category
- No prior therapy for AML other than hydroxyurea
- Judged by treating physician to be medically fit for induction chemotherapy
- Eastern Cooperative Oncology Group (ECOG) performance status score 0-2
- Normal left ventricular ejection fraction
Subjects will receive induction chemotherapy consisting of idarubicin 12 mg/m2 on Days 1-3 plus cytarabine 200 mg/m2 (age 18-59) or 100 mg/m2 (age 60-75) as a continuous IV infusion x 7 days. Volasertib will be administered on day 4 in a dose-escalation schedule, using a standard 3+3 dose escalation design, over 3 dose levels. Once the MTD has been determined, an additional dose expansion cohort will be accrued.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study treatment arm | Experimental | Drug: Volasertib, Drug: Idarubicin, Drug: CytarabineWill receive volasertib combined with idarubicin plus cytarabine in a 3+7 schedule as induction chemotherapy. Volasertib dose will be given on day 4 in a dose escalation schedule over 3 dose levels (140 mg/m2, 170 mg/m2, 200 mg/m2) in successive cohorts. Non-hematologic toxicity will be determined using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria for adverse events. Hematologic toxicity will be determined by days to absolute neutrophil count (ANC) and platelet recovery. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- AML, any World Health Organization (WHO) subtype except APL, either de novo or secondary; extramedullary AML (i.e. granulocytic sarcoma) is permitted.
- At least one of the following features:
- No prior therapy for AML other than hydroxyurea (allowed for up to 28 days). Prior therapy for MDS, MPD or other malignancy is allowed.
- Judged by treating physician to be medically fit for induction chemotherapy
- ECOG performance status score 0-2.
Key exclusion criteria (20 listed)
- Prior anthracycline exposure equivalent to > 300 mg/m2 doxorubicin.
- Prior chemotherapy or radiotherapy within previous four weeks except for hydroxyurea.
- Prior treatment with volasertib or any other Polo-like kinase inhibitor
- Known hypersensitivity to the trial drug
- Serum creatinine > 1.5 times (1.5x) upper limit of normal (ULN) or creatinine clearance (CLcr) < 30 ml/min (estimated creatinine clearance by the Cockcroft-Gault (C-G) equation
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 |
|---|---|---|
| VolasertibAlso: BI 6727Addition of single dose of volasertib intravenously (IV) on Day 4 of treatment protocol. | Drug | Study treatment arm |
| IdarubicinGiven IV daily on Days 1-3 of treatment protocol. | Drug | Study treatment arm |
| CytarabineAlso: Ara-CGiven IV daily as 24-hour continuous infusion on Day 1-7 of treatment protocol. | Drug | Study treatment arm |
Primary outcome
Toxicity profile
Time frame: Participants will be followed for duration of induction cycle (expected time 28-35 days) for toxicity.
Non-hematologic toxicities will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Hematologic toxicities will be assessed by determining number of days to neutrophil (ANC) recovery to >0.5 x10(9)/L or platelet recovery to >20 x10(9)/L.
Dose-limiting toxicity (DLT)
Time frame: Participants will be followed for duration of induction cycle (expected time 28-35 days) for DLT assessment.
DLT is defined as grade 3-4 non-hematologic toxicity (except grade 3 nausea, vomiting, mucositis or creatinine elevation due to tumor lysis syndrome, and grade 3-4 neutropenic infections and electrolyte abnormalities) using CTCAE version 4.0.Hematologic DLT is defined as ANC recovery to >0.5 x10(9)/L or platelet recovery to >20 x10(9)/L of > 42 days.
Maximum tolerated dose (MTD)
Time frame: Determined after completion of dose-escalation phase of study, which will take approx. 12-15 months.
MTD is defined as maximum dose of volasertib associated with < 2/6 DLTs at a given dose level.
1 secondary outcome
Complete response rate of regimen
Time frame: Responses will be determined at hematologic recovery (Day 28 or greater, up to Day 60).
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2017.
- Individual participant dataSharing planned: Yes. Anonymized data will be made available to Boehringer-Ingelheim.
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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.
Joseph Brandwein, MD principal investigator
University of Alberta
2 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 Volasertib, Idarubicin and Cytarabine in people with Leukemia, Myeloid, Acute and Leukemia, Monocytic, Acute, run by University of Alberta at 2 sites in Canada.
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 16 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: withdrawn, as of the sponsor's last update on 5 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Toxicity profile (time frame: Participants will be followed for duration of induction cycle (expected time 28-35 days) for toxicity.). The study lists 3 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 5 Apr 2017.