Clinical Trial: A Study of Volasertib Plus Induction Chemotherapy for Acute Myeloid Leukemia
Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional
Official Title: A Phase I Study of Volasertib Combined With Standard Induction Chemotherapy for Previously Untreated Patients With Acute Myeloid Leukemia (VIAC)
Brief 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).
Detailed Summary:
Main inclusion criteria:
- AML, any subtype except acute promyelocytic leukemia (APL)
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At least one of the following features:
i. 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.
Sponsor: University of Alberta
Current 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.
Original 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.
Current Secondary Outcome: Complete response rate of regimen [ Time Frame: Responses will be determined at hematologic recovery (Day 28 or greater, up to Day 60). ]
Original Secondary Outcome: Same as current
Information By: University of Alberta
Dates:
Date Received: July 6, 2015
Date Started: November 2016
Date Completion: September 2018
Last Updated: April 3, 2017
Last Verified: April 2017