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Acute Myeloid LeukemiaPhase 1NCT05744739

Tomivosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML)

A Phase 1 study testing Biospecimen Collection and Tomivosertib in people with Acute Myeloid Leukemia, run by Northwestern University 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

Phase 1 of the study will open first with a (Bayesian optimal interval BOIN) dose finding design. The starting dose of tomivosertib is 100mgdaily (doses 24 ± 2 hours apart), PO, self-administered with meals. The dose finding follows a BOIN design, with the 100mg BID dose level with a meal being the highest dose. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Biospecimen Collection and Tomivosertib
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
29 Sep 2023to 20 Aug 2024
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 age >= 18 years
  • Patients with relapsed/refractory AML (based on the International Consensus Classification of Myeloid Neoplasms and Acute Leukemias
  • Previous treatment must consist of:
  • At least 1 cycle of therapy with an anthracycline and standard dose cytarabine containing regimen; OR
  • At least one cycle of a high- or intermediate-dose cytarabine containing regimen; OR
  • At least 4 cycles of hypomethylating agent (HMA) as single agent or 2 cycles of HMA and venetoclax; OR
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  • Allogeneic stem cell transplant (SCT) for either AML or high-risk MDS and have recovered from all transplant-related toxicities, are off all immunosuppression for at least 6 weeks, and have no evidence of acute or chronic graft-versus-host disease GvHD); OR
  • Relapsed or refractory disease without established alternative therapy.
  • For patients with a known history of human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 6 months prior to registration.
  • For patients with a known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Patients must agree to serial bone marrow aspirate/biopsies
  • The effects of tomivosertib on the developing human fetus are unknown. For these reasons, patients of child-bearing potential (POCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) and refrain from donating eggs from the time of informed consent, for the duration of study treatment, and for 30 days following completion of study therapy. Should a patient become pregnant or suspect they are pregnant while they or their partner are participating in this study, they should inform their treating physician immediately.
  • People with sperm-producing reproductive capacity treated or enrolled on this protocol must also agree to use adequate contraception (or abstinence or vasectomy) and refrain from donating sperm from the time of informed consent, for the duration of study therapy, and 30 days after completion of study therapy.
  • NOTE: A POCBP is any person with an egg-producing reproductive tract (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy
  • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
  • POCBP (defined in 3.1.7) must have a negative serum β-subunit of human chorionic gonadotropin (β-hCG) pregnancy test (sensitivity of at least 25 mIU/mL) within 14 days prior to registration on study and have a negative serum β-hCG pregnancy test (sensitivity of at least 25 mIU/mL) within 72 hours prior to the start of study treatment.
  • NOTE: The screening serum pregnancy test can be used as the test prior to the start of study treatment if it is performed within the 72-hour timeframe.
  • Patients must provide written, signed, and dated informed consent prior to study registration. Patient must have the ability to understand and the willingness to sign a written informed consent document. The patient must be willing and able to comply with the protocol for the duration of the study. NOTE: No study-specific screening procedures may be performed until written consent has been obtained

Who cannot join

  • Patients who are receiving any other investigational agents
  • Previous chemotherapy including biologic/targeted therapy or immunological agents for AML within 14 days prior to start of tomivosertib..
  • Patients who have a prior or concurrent malignancy that may interfere with study treatment or safety. NOTE: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen (i.e., cancers under observation that do not require treatment, resectable skin cancer, low risk prostate cancer, DCIS, LCIS, etc.) are eligible per lead PI discretion. Patients with prior MDS or MPN are eligible.
  • Patients who have conditions that would interfere with drug absorption
  • Patients who have conditions that would interfere with their ability to swallow oral medications
  • Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to tomivosertib, azacitidine, and/or venetoclax
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  • Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
  • Uncontrolled systemic infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, antifungal therapy and/or other treatment)
  • Unstable angina pectoris
  • Cardiac ventricular arrhythmia, except for patients that can be successfully treated with rate control or anti-arrhythmic agents
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
  • Patients who are pregnant or nursing.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Northwestern University

    Chicago, Illinois, 60611

Other trials in United States

About this study

Official title: Phase 1 Dose Escalation Study of Tomivosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML)

Phase 1 of the study will open first with a (Bayesian optimal interval BOIN) dose finding design. The starting dose of tomivosertib is 100mgdaily (doses 24 ± 2 hours apart), PO, self-administered with meals. The dose finding follows a BOIN design, with the 100mg BID dose level with a meal being the highest dose. There is one dose level below (dose level -1 = 100mg QD without a meal) that will be given if the de-escalation condition is met during dose finding. Upon completion of the phase 1 dose finding portion of the study, the recommended starting dose of tomivosertib for the subsequent combination with the other agents will be determined, as described in Section 4.3 and Section 8.0.

Tomivosertib will be dosed continuously on days 1-28 of each 28-day cycle at the dose level assigned for that cohort.

Read the detailed description

PRIMARY OBJECTIVE:

To determine the dose of maximum pharmacologic activity (MPA) of tomivosertib in relapsed/refractory AML .

SECONDARY OBJECTIVES:

  1. To assess the adverse event profile of tomivosertib
  2. To estimate the rate of complete remission (CR)
  3. To estimate the rate of overall response
  4. To estimate the duration of response (DOR)
  5. To estimate progression free survival (PFS)
  6. To estimate overall survival (OS)
  7. To assess the outcomes for patients who undergo allogeneic hematopoietic stem cell transplant (HSCT)
  8. To assess the pharmacodynamics of tomivosertib by eIF4E phosphorylation before, during, and after cycle 1 treatment
  9. To measure MCL1 expression before and after cycle 1 treatment
  10. To assess the steady-state pharmacokinetics of tomivosertib

EXPLORATORY OBJECTIVES:

  1. To correlate eIF4E phosphorylation before and after cycle 1 treatment with treatment response.
  2. To correlate MCL1 expression before and after treatment with treatment response.
Being tested
Biospecimen Collection, Tomivosertib
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • TomivosertibDrug

    Also called EFT-508, eFT508, Spiro(cyclohexane-1,3'(2'H)-imidazo(1,5-a)pyridine)-1',5'-dione, 6'-((6-Amino-4-pyrimidinyl)amino)-8'-methyl-

    Given PO

Study groups in NCT05744739
Study groupRoleWhat they receive
Treatment (tomivosertib)ExperimentalTomivosertib will be dosed continuously on days 1-28 of each 28-day cycle.
Receives: Procedure: Biospecimen Collection; Drug: Tomivosertib

What is being measured

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

  1. Determine the dose of maximum pharmacologic activity (MPA) of tomivosertib

    The 'MPA' is defined as the minimum dose of tomivosertib tested in the phase 1 dose-finding portion of the trial that the isotonic estimate of dose-limiting toxicities (DLTs) is below or equal to the target DLT rate of 20% in phase 1 and biologic activity is observed. Whichever dose level is declared the MPA must have at least 6 patients treated at that level.

    Measured: From the initiation of trial therapy (cycle 1 day 1), and throughout the first cycle of treatment for a total of 28 days

Secondary outcomes (8)

  1. Frequency of adverse events

    Safety and tolerability will be summarized by providing a frequency of adverse events (CTCAE version 5.0) by severity, type, timing, and attribution for toxicities of any grade, with rates of >= grade 3 toxicities also analyzed separately. Adverse event rates will be summarized and accompanied by 95% exact binomial confidence intervals.

    Measured: Up to 18 months

  2. Overall response rate

    The proportion of treated patients who experience an objective response (complete remission [CR], complete remission with incomplete platelet recovery [CRp], complete remission with incomplete hematological recovery [CRi] and partial remission [PR]) per International Working Group AML Response Criteria. Will be summarized as a proportion with a corresponding exact 95% confidence interval (CI).

    Measured: Up to 18 months

  3. Complete remission rate (CRR)

    The proportion of treated patients who experience CR, CRp, and CRi will be reported. The first date of response for CR, CRp, or CRi will be used for the calculation of CRR. Will be summarized as a proportion with a corresponding exact 95% CI.

    Measured: Up to 18 months

  4. Duration of response (DOR)

    Will be analyzed using the Kaplan-Meier method. The median of DOR, if estimable, will be reported along with the confidence intervals.

    Measured: Time between the day of first documented response to trial therapy (CR, CRp, and CRi or PR), whichever is first recorded, and subsequent disease progression, assessed up to 18 months

  5. Progression free survival (PFS)

    Will be analyzed using the Kaplan-Meier method. The median of PFS, if estimable, will be reported along with the confidence intervals.

    Measured: Time between the initiation of trial therapy and the day of first documented disease progression or death from any cause, assessed up to 18 months

  6. Overall survival (OS)

    Will be analyzed using the Kaplan-Meier method. The median of OS, if estimable, will be reported along with the confidence intervals.

    Measured: Time between the initiation of trial therapy and the date of death from any cause, assessed up to 18 months

  7. To assess the pharmacodynamics of tomivosertib by eIF4E phosphorylation before, during, and after cycle 1 treatment

    Phosphorylation of eIF4E will be assessed by flow cytometry in order to identify a biologically effective dose.

    Measured: Baseline and after Cycle 1 treatment

  8. OS for patients who proceed to transplant

    Will estimate the OS for patients who proceed to transplant, compared to those who do not undergo transplant.

    Measured: From initiation of therapy until the patient completes follow-up, or experiences death from any cause, assessed up to 18 months

Timeline

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

  1. First posted27 Feb 2023
  2. Study start29 Sep 2023
  3. Primary completion29 Jul 2024
  4. Study completion20 Aug 2024

Why it stopped: Premature withdrawal of investigational product per study sponsor.

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
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05744739
Sponsor's protocol ID
NU 22H08
Other IDs
NCI-2023-00767, NU 22H08, STU00218776, P30CA060553
Status last verified
Jun 2026
First submitted
16 Feb 2023
Last updated
11 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biospecimen Collection and Tomivosertib in people with Acute Myeloid Leukemia, run by Northwestern University 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 20 inclusion and 13 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 11 Jun 2026. 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: Premature withdrawal of investigational product per study sponsor.). 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?

Determine the dose of maximum pharmacologic activity (MPA) of tomivosertib (time frame: From the initiation of trial therapy (cycle 1 day 1), and throughout the first cycle of treatment for a total of 28 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 NCT05744739.

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 11 Jun 2026.

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