Clinical Trials /

Volasertib Combined With Induction Chemotherapy in Acute Myeloid Leukemia

NCT02905994

Description:

The study intervention involved in this study is the addition of a dose of volasertib as a part of the initial chemotherapy regimen for AML. The trial will involve a combination of the following drugs: - Volasertib (the study drug) - Idarubicin - Cytarabine

Related Conditions:
  • Acute Myeloid Leukemia
  • Acute Promyelocytic Leukemia
Recruiting Status:

Withdrawn

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Volasertib Combined With Induction Chemotherapy in Acute Myeloid Leukemia
  • Official Title: A Phase I Trial of Volasertib (BI 6727), an Intravenous Polo-Like Kinase Inhibitor, in Combination With "7+3" Induction Chemotherapy for Patients With Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 16-299
  • NCT ID: NCT02905994

Conditions

  • AML

Interventions

DrugSynonymsArms
VolasertibBI 6727Volasertib with chemotherapy
CytarabineDepocytVolasertib with chemotherapy
IdarubicinIdamycinVolasertib with chemotherapy

Purpose

The study intervention involved in this study is the addition of a dose of volasertib as a part of the initial chemotherapy regimen for AML. The trial will involve a combination of the following drugs: - Volasertib (the study drug) - Idarubicin - Cytarabine

Detailed Description

      This research study is a Phase I clinical trial, which tests the safety of an investigational
      drug and also tries to define the appropriate dose of the investigational drug to use for
      further studies. "Investigational" means that the drug is being studied.

      As part of this research study, the participant will receive Volasertib in combination with
      two other chemotherapy drugs, Idarubicin and Cytarabine. The FDA (the U.S. Food and Drug
      Administration) has not approved volasertib as a treatment for any disease.

      Idarubicin and Cytarabine are chemotherapy agents that are commonly used to treat individuals
      diagnosed with AML. Volasertib inhibits proteins called "polo-like kinases," which are
      necessary for cell division. Volasertib binds to these proteins and this inhibits the growth
      of cancer cells. Volasertib has been used in laboratory studies and those studies suggest
      that volasertib may slow down the growth of Cancer. In a previous clinical trial in patients
      with the participant type of leukemia where Volasertib was given along with low doses of
      Cytarabine, this drug was found to have some clinical activity against AML. In this study,
      researchers would like to combine Volasertib with standard chemotherapy (Cytarabine and
      Idarubicin) in order to see if it can be given safely with chemotherapy in individuals with
      AML.

      The primary purpose of this research study is to determine the highest dose that Volasertib
      can be given with Idarubicin and Cytarabine without severe or unmanageable side effects. The
      dose identified in this study will be used in future research studies.
    

Trial Arms

NameTypeDescriptionInterventions
Volasertib with chemotherapyExperimentalPatients enrolled on this trial will receive induction chemotherapy with "7+3" Cytarabine continuous infusion days 1-7 Idarubicin IV bolus on days 1, 2, and 3. Patients will receive Volasertib as an intravenous infusion over approximately 1 hour, according to dosing level, on day 8 Patients will receive Standard Anti Fungal and Standard Antibiotic during induction A bone marrow biopsy will be performed according to standard practice on day 14
  • Volasertib
  • Cytarabine
  • Idarubicin

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have pathologically confirmed, newly diagnosed acute myeloid
             leukemia.

          -  Adults, age 18 years or older at the time of diagnosis, eligible for standard
             induction chemotherapy according to their treating physician.

          -  ECOG performance status 0-2 (Karnofsky ≥60%, see Appendix A)

          -  Left ventricular ejection fraction > 50% as measured by echocardiogram or MUGA scan

          -  Must not have received systemic antineoplastic therapy including radiation therapy
             within 14 days of the study enrollment, except hydroxyurea or 6-mercaptopurine for the
             purposes of cytoreduction as per the treating physician. Patients may also have
             received all-trans retinoic acid (ATRA) if there is an early suspicion of acute
             promyelocytic leukemia (APL, M3-AML), although if confirmed to have APL these patients
             will be excluded from the study.

          -  Female patients of childbearing age must have negative pregnancy test.

          -  Participants must have normal organ and marrow function as defined below:

               -  total bilirubin < 3 times the ULN

               -  creatinine within normal institutional limits OR

               -  creatinine clearance ≥30 mL/min/1.73 m2 for participants with creatinine levels
                  above institutional normal.

          -  The effects of volasertib (BI 6727) on the developing human fetus are unknown. For
             this reason and because other chemotherapeutic agents are known to be teratogenic,
             women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation, and 6 months after completion of therapy. Should
             a woman become pregnant or suspect she is pregnant while she or her partner is
             participating in this study, she should inform her treating physician immediately. Men
             treated or enrolled on this protocol must also agree to use adequate contraception for
             the duration of study participation, and 6 months after completion of therapy.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Patients will be excluded from this study if they are found to harbor "favorable" risk
             cytogenetics41 including:

               -  APL, t(15;17)

               -  t(8;21)

               -  inv(16) or t(16;16) A sample to evaluate patient cytogenetics will be sent at the
                  time of diagnosis per standard clinical care and the absence of these
                  cytogenetics must be confirmed by Day 8. If the cytogenetic analysis reveals that
                  the patient harbors favorable risk cytogenetics, or if the cytogenetic results
                  are not received prior to Day 8, the participant will be removed from the study.

          -  Patients with acute bilineal/biphenotypic leukemia

          -  Participants who have had chemotherapy or radiotherapy within 14 days prior to
             entering the study, except for hydroxyurea, 6-MP, and ATRA, as noted.

          -  Participants who are receiving any other investigational agents.

          -  Chemo-, hormono-, radio- or immunotherapy or therapy with monoclonal antibodies or
             small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the
             trial drug

          -  Persistence of clinically relevant therapy related toxicity from previous anti-cancer
             therapy

          -  Prior allogeneic bone marrow or organ transplantation

          -  Individuals with a history of a different malignancy are ineligible except for the
             following circumstances. Individuals with a history of other malignancies are eligible
             if they have been disease-free for at least 5 years and are deemed by the investigator
             to be at low risk for recurrence of that malignancy. Individuals with the following
             cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer
             in situ, and basal cell or squamous cell carcinoma of the skin.

          -  Current clinical central nervous system (CNS) symptoms deemed by the investigator to
             be related to leukemic CNS involvement (no lumbar puncture required, clinical
             assessment per investigator's judgment is sufficient).

          -  Prior treatment with volasertib or another polo-like kinase inhibitor

          -  A diagnosis of active Hepatitis B or C infection. A patient with a prior infection may
             participate, so long as the infection is not active at the time of study screening
             tests and according to investigator discretion.

          -  Current or history of ventricular or life-threatening arrhythmias or diagnosis of
             long-QT syndrome. Baseline QTc must be 470 msec or less, according to the Friderica
             correction method,42 calculated as the mean of 3 ECGs taken at the time of screening.

          -  Current or history of congestive heart failure New York Heart Association (NYHA) class
             3 or 4, or any history of documented diastolic or systolic dysfunction (LVEF <50%, as
             measured by MUGA scan or echocardiogram).

          -  Known hypersensitivity to the trial drugs or other contraindication to standard "7+3"
             induction chemotherapy.

          -  Although not absolute exclusion criteria, several known drug-drug interactions should
             be considered during enrollment (see Section 5.5).

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study because volasertib, along with standard
             induction chemotherapy, carries the potential for teratogenic or abortifacient
             effects. Because there is an unknown but potential risk for adverse events in nursing
             infants secondary to treatment of the mother with volasertib as well as cytarabine and
             idarubicin, breastfeeding should be avoided.

          -  HIV-positive participants on combination antiretroviral therapy are ineligible because
             of the potential for pharmacokinetic interactions with volasertib. In addition, these
             participants are at increased risk of lethal infections when treated with
             marrow-suppressive therapy.

          -  Patients with psychological, familial, social, or geographic factors that otherwise
             preclude them from giving informed consent, following the protocol, or potentially
             hamper compliance with study treatment and follow-up.

          -  Patients who are otherwise felt unable to comply with the protocol, in the opinion of
             the investigator.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Establishing The Maximum Tolerated Dose (MTD)
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Rate of Complete Response
Time Frame:2 years
Safety Issue:
Description:
Measure:Rate of Relapse Free Survival
Time Frame:1 year
Safety Issue:
Description:
Measure:Rate of Overall Survival
Time Frame:1 year
Safety Issue:
Description:
Measure:Rate of partial response
Time Frame:2 years
Safety Issue:
Description:
Measure:Degree of change in the presence of subclones with Disease Response
Time Frame:2 years
Safety Issue:
Description:Measured by subclonal disease evolution, during treatment with volasertib and "7+3"
Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Withdrawn
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Leukemia

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