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Recurrent Acute Myeloid LeukemiaPhase 1NCT05441514

Enasidenib in Combination With Cobimetinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1 study testing Cobimetinib and Enasidenib Mesylate in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by City of Hope Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase Ib trial tests the safety, side effects, and best dose of a enasidenib in combination with cobimetinib in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cobimetinib and Enasidenib Mesylate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
28 Apr 2023to 19 Mar 2026
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

Main Inclusion Criteria

  • Patients with histologically confirmed AML, according to WHO criteria, with refractory/relapsed (R/R) disease who are ineligible for therapies known to be effective for treatment of their AML.
  • Patients with non-central nervous system (CNS) extramedullary disease may be included if they also have marrow involvement
  • Patients with acute promyelocytic leukemia (APL) will not be eligible
  • Patients with IDH2 mutations, who were previously treated with enasidenib are allowed
  • Have a documented IDH2 gene mutation (≥ 2% allele frequency) and a concomitant detectable RAS-pathway mutation (as determined by local testing), involving NRAS, KRAS, HRAS, BRAF, KIT, RIT1, PTPN11, CBL or NF1 genes.
  • Adults aged ≥ 18 years
  • ECOG ≤ 2
  • WBC ≤25 x 10^9/L prior to initiation of enasidenib.

Main Exclusion Criteria

  • Current or planned use of other investigational agents, antineoplastic, chemotherapy, radiation therapy, biological therapy, immunotherapy or major surgery within 2 weeks or 5 half-lives, whichever is shorter, prior to Day 1 of protocol therapy (exception: hydroxyurea is allowed in cycles 1 and 2 for control of rapidly progressing leukemia or for treatment of enasidenib-related leukocytosis)
  • Systemic steroid therapy > 10 mg/day (≤ 10mg/day prednisone equivalent ok) or any other form of immunosuppressive medication within 28 days, except as required for treatment of differentiation syndrome
  • Strong and moderate CYP3A4 inducers/inhibitors (moderate CYP3A4 inhibitors only allowed on Principal Investigator approval) within 14 days or 5 half-lives, whichever is shorter, prior to Day 1 of protocol therapy
  • Foods/supplements that are strong or moderate inhibitors or inducers of CYP3A (such as grapefruit, Seville oranges, starfruit and St. John's wort) within 7 days prior to initiation of and during study treatment
  • Gastrointestinal disorder such as maladsorption syndrome or any other disorder that may interfere with oral drug absorption
  • Clinically significant cardiac morbidities (Class III/IV cardiovascular disability according to the New York Heart Association Classification, arrhythmia not stable on medical management, acute cardiovascular ischemic event within 6 months of enrollment, etc)
  • Active CNS disease

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: Phase 1b Study of IDH Inhibition With Enasidenib and MEK Inhibition With Cobimetinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia Who Have Co-Occurring IDH2 and RAS Signaling Gene Mutations

This phase Ib trial tests the safety, side effects, and best dose of a enasidenib in combination with cobimetinib in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). Enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Cobimetinib is used in patients whose cancer has a mutated (changed) form of a gene called BRAF. It is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving enasidenib and cobimetinib may kill more cancer cells in patients with relapsed or refractory acute myeloid leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Assess the safety and tolerability of cobimetinib in combination with enasidenib.

II. Determine the maximum tolerated dose(s) (MTD) and recommended phase 2 dose (RP2D).

SECONDARY OBJECTIVES:

  1. Obtain preliminary estimates of clinical activity as measured by the complete remission (complete response [CR], complete response with incomplete hematologic recovery [CRi], or complete response with partial hematologic recovery [CRh]) rate and minimal residual disease (MRD) rate.

II. Obtain preliminary estimates of clinical activity as measured by overall response rate (CR, CRi, CRh, morphologic leukemia free state [MLFS], and partial response [PR]).

III. Obtain preliminary estimates of median time to complete remission. IV. Obtain preliminary estimates of median time to first response. V. Obtain preliminary estimates of response duration in all participants and in those attaining CR/CRi/CRh.

VI. Obtain preliminary estimates of median and 1-year event-free survival (EFS).

VII. Obtain preliminary estimates of median and 1-year overall survival (OS).

EXPLORATORY OBJECTIVES:

  1. Characterize the effects of the combination on cellular differentiation of leukemic cells as measured by flow cytometry performed at study entry and at serial timepoints throughout the study.

II. Evaluate changes in promotor methylation patterns after treatment with combination therapy.

III. Evaluate changes in gene expression of RAS pathway regulators as a result of the combination therapy.

OUTLINE: This is dose-escalation study of cobimetinib followed by a dose-expansion study.

Patients receive cobimetinib orally (PO) once daily (QD) on days 1-21 and enasidenib mesylate PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and every 3 months for 1 year at last treatment dose.

Being tested
Cobimetinib, Enasidenib Mesylate
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.

  • CobimetinibDrug

    Also called Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518

    Given PO

  • Enasidenib MesylateDrug

    Also called 2-Methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol Methanesulfonate, 2-Propanol, 2-Methyl-1-((4-(6-(trifluoromethyl)-2-pyridinyl)-6-((2-(trifluoromethyl)-4-pyridinyl)amino)-1,3,5-triazin-2-yl)amino)-, Methanesulfonate (1:1), AG-221 Mesylate, CC-90007

    Given PO

Study groups in NCT05441514
Study groupRoleWhat they receive
Treatment (cobimetinib, enasidenib mesylate)ExperimentalPatients receive cobimetinib PO QD on days 1-21 and enasidenib mesylate PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cobimetinib; Drug: Enasidenib Mesylate

What is being measured

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

  1. Dose limiting toxicity

    Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

    Measured: Cycle 1 (28 days)

  2. Incidence of adverse events

    Toxicity will be graded according to the NCI- CTCAE version 5.0. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.

    Measured: Up to 30 days after last dose of study drug

Secondary outcomes (7)

  1. Response

    Response will be determined using European LeukemiaNet (ELN) criteria.

    Measured: Up to 1 year

  2. Minimal residual disease (MRD) status

    MRD status will be determined by standard of care (SOC) flow cytometry assay.

    Measured: Up to 1 year

  3. Complete remission

    Time to complete remission is defined as time from first study dose to attainment of complete response(CR), complete response with incomplete hematologic recovery CRi, or complete response with partial hematologic recovery CRh). Will calculate rates and 95% Clopper-Pearson binomial confidence interval (CI).

    Measured: Up to 1 year

  4. Time to first response

    Time to first response is defined as time from first study dose to attainment of first documented CR, CRi, CRh, morphologic leukemia free state (MLFS), or partial response (PR). Will calculate rates and 95% Clopper-Pearson binomial CI.

    Measured: From first study does to first documented complete response, assessed up to 3 years

  5. Response duration

    Response Duration is defined as the time from the date of first documented response (CR, CRi, CRh, MLFS or PR) to documented disease relapse/progression or death, whichever occurs first. Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: From first study does to first documented complete response, assessed up to 1 year

  6. Event-free survival (EFS)

    Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: From first study dose to first documented complete response to relapse/progression (> 5% blasts, reappearance of blasts in blood, or development of extramedullary disease) or death, whichever occurs first, assessed up to 1 year

  7. Overall survival (OS)

    Will be estimated using the product-limit method of Kaplan and Meier.

    Measured: From first study dose to death from any cause, assessed up to 1 year

Timeline

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

  1. First posted1 Jul 2022
  2. Study start28 Apr 2023
  3. Primary completion19 Mar 2026
  4. Study completion19 Mar 2026

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
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05441514
Sponsor's protocol ID
21751
Other IDs
NCI-2022-04926, 21751, P30CA033572
Status last verified
Apr 2026
First submitted
28 Jun 2022
Last updated
5 May 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 Cobimetinib and Enasidenib Mesylate in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by City of Hope Medical Center 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?

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: finished, as of the sponsor's last update on 5 May 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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: Cycle 1 (28 days)). The study lists 2 primary outcomes in all. 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 NCT05441514.

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 5 May 2026.

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