A Study of Volasertib Plus Induction Chemotherapy for Acute Myeloid Leukemia

NCT02527174 | Withdrawn Phase 1 DMC

• 1 other identifier: 1230-37
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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).

Conditions

Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Determined after completion of dose-escalation phase of study, which will take approx. 12-15 months.

Secondary Outcomes (1)

• Complete response rate of regimen

  Responses will be determined at hematologic recovery (Day 28 or greater, up to Day 60).

Study Arms (1)

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.

Drug: Volasertib; Drug: Idarubicin; Drug: Cytarabine

Interventions

Volasertib DRUG

Addition of single dose of volasertib intravenously (IV) on Day 4 of treatment protocol.

Also known as: BI 6727

Study treatment arm

Idarubicin DRUG

Given IV daily on Days 1-3 of treatment protocol.

Study treatment arm

Cytarabine DRUG

Given IV daily as 24-hour continuous infusion on Day 1-7 of treatment protocol.

Also known as: Ara-C

Study treatment arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• q23 abnormality
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (2)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2G3, Canada

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute

Interventions

BI 6727; Idarubicin; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Joseph Brandwein, MD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Division of Hematology

Study Record Dates

• First Submitted: July 6, 2015
• First Posted: August 18, 2015
• Study Start: November 1, 2016
• Primary Completion: May 1, 2018
• Study Completion: September 1, 2018
• Last Updated: April 5, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will share

Locations

CA (2)