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A Study of Volasertib Plus Induction Chemotherapy for Acute Myeloid Leukemia (VIAC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02527174
Recruitment Status : Withdrawn (Volasertib no longer available)
First Posted : August 18, 2015
Last Update Posted : April 5, 2017
Sponsor:
Information provided by (Responsible Party):
Joseph Brandwein, University of Alberta

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).

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Leukemia, Monocytic, Acute Leukemia, Myelomonocytic, Acute Leukemia, Erythroblastic, Acute Leukemia, Megakaryoblastic, Acute Drug: Volasertib Drug: Idarubicin Drug: Cytarabine Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Volasertib Combined With Standard Induction Chemotherapy for Previously Untreated Patients With Acute Myeloid Leukemia (VIAC)
Study Start Date : November 2016
Estimated Primary Completion Date : May 2018
Estimated Study Completion Date : September 2018


Arm Intervention/treatment
Experimental: Study treatment arm

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
Addition of single dose of volasertib intravenously (IV) on Day 4 of treatment protocol.
Other Name: BI 6727

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

Drug: Cytarabine
Given IV daily as 24-hour continuous infusion on Day 1-7 of treatment protocol.
Other Name: Ara-C




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. AML, any World Health Organization (WHO) subtype except APL, either de novo or secondary; extramedullary AML (i.e. granulocytic sarcoma) is permitted.
  2. 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
      • 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
  3. No prior therapy for AML other than hydroxyurea (allowed for up to 28 days). Prior therapy for MDS, MPD or other malignancy is allowed.
  4. Judged by treating physician to be medically fit for induction chemotherapy
  5. ECOG performance status score 0-2.
  6. Left ventricular ejection fraction (LVEF) within normal limits, by myocardial multigated scan (MUGA) or echocardiogram.
  7. Signed and dated written informed consent prior to admission

Exclusion Criteria:

  1. Prior anthracycline exposure equivalent to > 300 mg/m2 doxorubicin.
  2. Prior chemotherapy or radiotherapy within previous four weeks except for hydroxyurea.
  3. Prior treatment with volasertib or any other Polo-like kinase inhibitor
  4. Known hypersensitivity to the trial drug
  5. 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
  6. Serum bilirubin > 1.5x ULN, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3x ULN
  7. Persistence of clinically relevant therapy related toxicity from previous anti-cancer therapy
  8. Active central nervous system leukemia (no lumbar puncture required; clinical judgement is sufficient)
  9. 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
  10. 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)
  11. 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.
  12. Other concurrent malignancy requiring active therapy (except hormonal therapy for prostate or breast cancer).
  13. Severe uncontrolled infection. Controlled infection on antibiotics is permitted.
  14. Active or chronic hepatitis C and/or B infection
  15. Known HIV infection
  16. 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.
  17. 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.
  18. Pregnancy or breast feeding, female patients must have a negative pregnancy test prior to commencing study treatment.
  19. Psychological, familial or sociological factors potentially hampering compliance with the study protocol and follow-up schedule
  20. Known or suspected active alcohol or drug abuse

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02527174


Locations
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Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N 4N2
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 2G3
Sponsors and Collaborators
University of Alberta
Investigators
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Principal Investigator: Joseph Brandwein, MD University of Alberta
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Responsible Party: Joseph Brandwein, Director, Division of Hematology, University of Alberta
ClinicalTrials.gov Identifier: NCT02527174    
Other Study ID Numbers: 1230-37
First Posted: August 18, 2015    Key Record Dates
Last Update Posted: April 5, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized data will be made available to Boehringer-Ingelheim.
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Acute
Leukemia, Erythroblastic, Acute
Leukemia, Monocytic, Acute
Leukemia, Megakaryoblastic, Acute
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Cytarabine
Idarubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors