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AMLPhase 1NCT02905994

Volasertib Combined With Induction Chemotherapy in Acute Myeloid Leukemia

A Phase 1 study testing Volasertib, Cytarabine and Idarubicin in people with AML, run by Massachusetts General Hospital at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
AML
What is being tested?
Volasertib, Cytarabine and Idarubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesUnited States
Study dates
Sep 2016to Feb 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts general Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02115

Other trials in United States

About this study

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

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
Read the 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.

Conditions
AML
Being tested
Volasertib, Cytarabine, Idarubicin, Bone Marrow Biopsy
Keywords
Leukemia
Medical subject headings
Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VolasertibDrug

    Also called BI 6727

    Polo-Like Kinase Inhibitor

  • CytarabineDrug

    Also called Depocyt

    Standard chemotherapy at dosage and schedule for 7+3 induction

  • IdarubicinDrug

    Also called Idamycin

    Standard chemotherapy at dosage and schedule for 7+3 induction

  • Bone Marrow BiopsyProcedure or surgery

    Bone marrow biopsy assessments scheduled during induction to assess response

Study groups in NCT02905994
Study groupRoleWhat they receive
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
Receives: Drug: Volasertib; Drug: Cytarabine; Drug: Idarubicin; Procedure: Bone Marrow Biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Establishing The Maximum Tolerated Dose (MTD)

    Measured: 2 years

Secondary outcomes (6)

  1. Rate of Complete Response

    Measured: 2 years

  2. Rate of Relapse Free Survival

    Measured: 1 year

  3. Rate of Overall Survival

    Measured: 1 year

  4. Rate of partial response

    Measured: 2 years

  5. Degree of change in the presence of subclones with Disease Response

    Measured by subclonal disease evolution, during treatment with volasertib and "7+3"

    Measured: 2 years

  6. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2016 (estimated)
  2. Study startSep 2016
  3. Primary completionFeb 2017
  4. Study completionFeb 2017

Why it stopped: Funding Withdrawn

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02905994
Sponsor's protocol ID
16-299
Status last verified
May 2018
First submitted
12 Sep 2016
Last updated
4 May 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Volasertib, Cytarabine and Idarubicin in people with AML, run by Massachusetts General Hospital at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 4 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Establishing The Maximum Tolerated Dose (MTD) (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02905994.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2018.

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