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Study Status: Withdrawn
Recruit Status: Withdrawn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:

  1. AML, any subtype except acute promyelocytic leukemia (APL)

  2. 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

  3. No prior therapy for AML other than hydroxyurea
  4. Judged by treating physician to be medically fit for induction chemotherapy
  5. Eastern Cooperative Oncology Group (ECOG) performance status score 0-2
  6. 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). ]

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.


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