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Acute Myeloid LeukemiaPhase 1NCT03735446

Prexasertib in Combination With MEC in Relapsed/Refractory AML and High Risk MDS - a Phase I Trial

A Phase 1 study testing Prexasertib, Mitoxantrone and Etoposide in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Dana-Farber Cancer Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This research study is studying a targeted therapy combined with chemotherapy as a possible treatment for acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS). The drugs involved in this study are: Prexasertib (LY2606368) Mitoxantrone Etoposide Cytarabine Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Prexasertib, Mitoxantrone and Etoposide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
18 Jan 2019to 29 Mar 2019
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

  • Patients must have histologically confirmed relapsed or refractory acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS) diagnosed per WHO criteria.
  • For refractory AML: refractory as defined per International Working Group (IWG) criteria. Refractory patients must have had ≤ 2 prior induction regimens (hydroxyurea is not considered a prior treatment regimen). "5+2" reinduction at day 14 is not considered a second regimen.
  • For relapsed AML: relapse as defined by IWG criteria. Relapsed patients must be first or second relapse (hydroxyurea is not considered a prior treatment regimen).
  • For patients with MDS, ≥ 10% myeloblasts in the bone marrow, and no more than 2 prior treatment regimens (hydroxyurea is not considered a prior treatment regimen).
  • Patients must be medically eligible to receive mitoxantrone, etoposide, and cytarabine (MEC) therapy.
  • Age ≥ 18 years
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  • ECOG performance status ≤ 2 (Karnofsky ≥60%)
  • Patients must have adequate organ function as defined below:
  • Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN), OR
  • Total bilirubin ≤ 2 × institutional ULN if the participant has a history of Gilbert's syndrome.
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN, OR
  • AST(SGOT)/ALT(SGPT) ≤ 5 × institutional ULN if elevation is a result of leukemia
  • Serum creatinine ≤ 1.5 × institutional ULN, OR
  • Creatinine Clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal (calculated via the Cockcroft-Gault equation).
  • Left ventricular ejection fraction (LVEF) ≥ 50% on screening echocardiogram (ECHO) or multigated acquisition scan (MUGA).
  • QTcF value of ≤ 450 msec on screening electrocardiogram (ECG).
  • Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after treatment. 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 prior to the study, for the duration of study participation, and 4 months after completion of study therapy administration. A negative serum pregnancy test is required for women of child-bearing potential.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Patients may have had a prior autologous or allogeneic transplant if there is at least 100 days between transplant and screening, and there is no evidence of active graft-versus-host-disease (GvHD) or ongoing requirement for immunosuppressive therapy.

Who cannot join

  • Patients who have had chemotherapy, other investigational therapy, radiotherapy, or immune therapy within 2 weeks prior to the first dose of study medication. Hydroxyurea is allowed with no required washout and may be administered up to day 5 of protocol therapy.
  • Patients previously treated with MEC chemotherapy.
  • Patients who have received a tyrosine kinase inhibitor (TKI) within 5 half-lives of day 1.
  • Patients who have had major surgery within 4 weeks prior to the first dose of study medication.
  • Patients with acute promyelocytic leukemia.
  • Patients with a known personal or family history of long QT syndrome.
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  • Patients with known CNS leukemia involvement.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to prexasertib, mitoxantrone, etoposide, or cytarabine.
  • Patients with a history of a secondary malignancy, with the following exceptions:
  • Malignancies that have been curatively treated and have not recurred within the past 2 years
  • Adequately treated carcinoma in situ of any type
  • Curatively treated non-melanoma skin cancers
  • Any other malignancy that has been curatively treated with a low likelihood of recurrence as judged by the treating investigator and agreed upon with the overall principal investigator prior to study entry
  • Patients with other secondary malignancies may be allowed to enroll with agreement from the overall principal investigator.
  • Uncontrolled intercurrent illness including, but not limited to: uncontrolled active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because prexasertib, mitoxantrone, etoposide, and cytarabine are anti-cancer agents with 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 the study agents, breastfeeding should be discontinued if the mother is treated with prexasertib, mitoxantrone, etoposide, or cytarabine.
  • Patients who are known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B or C.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Prexasertib in Combination With Mitoxantrone, Etoposide and Cytarabine (MEC) in Relapsed/Refractory Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS) - a Phase I Trial

This research study is studying a targeted therapy combined with chemotherapy as a possible treatment for acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS).

The drugs involved in this study are:

  • Prexasertib (LY2606368)
  • Mitoxantrone
  • Etoposide
  • Cytarabine
Read the detailed description

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

The FDA (the U.S. Food and Drug Administration) has not approved prexasertib as a treatment for any disease. Prexasertib is a checkpoint kinase 1 (CHK1) inhibitor that is being developed as a treatment for patients with advanced cancer. CHK1 inhibitors work by preventing cancer cells from being able to repair damaged DNA (one of the building blocks of a cell) which then leads to cell death.

The drugs mitoxantrone, etoposide, and cytarabine (MEC) have all been approved by the FDA. MEC is a standard chemotherapy treatment option, commonly used for AML that has not responded to other standard treatment or returned following standard treatment.

In this research study, the investigators are combining prexasertib with MEC therapy to test if it is a safe treatment for AML or MDS that has returned or not responded to standard treatment.

Being tested
Prexasertib, Mitoxantrone, Etoposide, Cytarabine
Keywords
Acute Myeloid Leukemia, Myelodysplastic Syndromes, AML, MDS, CHK1, MEC, Prexasertib
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

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

  • PrexasertibDrug

    Also called LY2606368

    Checkpoint kinase 1 (CHK1) inhibitor

  • MitoxantroneDrug

    Also called Novantrone

    Standard chemotherapy (topoisomerase inhibitor)

  • EtoposideDrug

    Standard chemotherapy (topoisomerase II inhibitor)

  • CytarabineDrug

    Standard chemotherapy (anti-metabolite)

Study groups in NCT03735446
Study groupRoleWhat they receive
Prexasertib+MECExperimental* Cytarabine is administered intravenously on days 1-5. * Etoposide is administered intravenously on days 1-5. * Mitoxantrone is administered intravenously on days 1-5. * Prexasertib is administered intravenously on days 1, 3, and 5.
Receives: Drug: Prexasertib; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine

What is being measured

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

  1. Dose Limiting Toxicity

    Toxicities occurring following administration of protocol therapy, measured using CTCAE 5.0 criteria.

    Measured: Up to 42 days

Secondary outcomes (4)

  1. Phase 2 Dose

    Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the study drug combination.

    Measured: 18 months

  2. Overall Response

    Rates of complete remission (CR), complete remission with incomplete count recovery (CRi), and partial remission (PR).

    Measured: 30 months

  3. Overall Survival

    Assess the overall survival rate for the combination.

    Measured: 30 months

  4. Duration of Remission

    Time of achievement of CR or CRi to relapse, death, or 1 year (whichever occurs first)

    Measured: 12 months

Timeline

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

  1. First posted8 Nov 2018
  2. Study start18 Jan 2019
  3. Primary completion29 Mar 2019
  4. Study completion29 Mar 2019

Why it stopped: Sponsor Decision

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
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03735446
Sponsor's protocol ID
18-468
Status last verified
Jun 2019
First submitted
7 Nov 2018
Last updated
12 Jun 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Prexasertib, Mitoxantrone and Etoposide in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Dana-Farber Cancer Institute at 1 site 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 19 inclusion and 17 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: stopped early, as of the sponsor's last update on 12 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 stopped early (reason given: Sponsor Decision). Results are not available in the source record.

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?

Dose Limiting Toxicity (time frame: Up to 42 days). 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 NCT03735446.

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 12 Jun 2019.

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