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Recurrent Acute Myeloid LeukemiaPhase 2NCT04203316

Enasidenib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia Patients With an IDH2 Mutation

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by Children's Oncology Group at 28 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase II trial studies the side effects of enasidenib and sees how well it works in treating pediatric patients with acute myeloid leukemia that has come back after treatment (relapsed) or has been difficult to treat with chemotherapy (refractory). Read more about this study

Who is it for?
Ages 24 months to 21 years
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
28 sitesin 2 countries
Study dates
14 Aug 2023to 3 Oct 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 24 months to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients must be >= 24 months and < 21 years of age at the time of study enrollment
  • Patient must have AML with an IDH2 mutation identified from a peripheral blood or bone marrow sample at the time of diagnosis and/or relapsed/refractory disease
  • Patient must have bone marrow assessment (aspiration or biopsy) with > 5% leukemic blasts by morphology and/or flow cytometry in at least one of the following clinical scenarios:
  • Second or greater relapse after chemotherapy or hematopoietic stem cell transplant (HSCT)
  • Refractory after >= 2 attempts at induction therapy
  • Relapsed patients
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  • Must not have received prior re-induction therapy for this relapse
  • Each block of chemotherapy (i.e., cytarabine, daunorubicin and etoposide [ADE], cytarabine and mitoxantrone [MA]) is a separate re-induction attempt
  • Donor lymphocyte infusion (DLI) is considered a re-induction attempt
  • Refractory patients
  • Each attempt at induction therapy may include up to two chemotherapy courses
  • Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • Evaluation of cerebrospinal fluid (CSF) is only required if there is a clinical suspicion of central nervous system (CNS) involvement by leukemia during eligibility screening. Should a patient be found to have CNS2 or CNS3 status by CSF prior to eligibility screening, patient may receive intrathecal chemotherapy > 72 hours prior to starting study drug. CNS1 status must be established before starting study drug
  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
  • Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
  • >= 14 days must have elapsed after the completion of other cytotoxic therapy with the exception of hydroxyurea. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy. NOTE: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy
  • Intrathecal chemotherapy must be completed >= 72 hours prior to the start of the first cycle of treatment
  • Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
  • Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
  • Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
  • Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study research coordinator
  • Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
  • Stem cell Infusions (with or without total body irradiation [TBI]):
  • Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
  • >= 60 days after infusion for bone marrow or stem cell transplant and
  • >= 4 weeks after infusion for any stem cell infusion including DLI or boost infusion
  • There must be no evidence of graft versus host disease (GVHD)
  • Autologous stem cell infusion including boost infusion: >= 42 days
  • Cellular Therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
  • XRT/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
  • Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-metaiodobenzylguanidine [MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
  • Study-specific limitations on prior therapy: small molecule investigational agents: >= 14 days or > 5 half-lives must have elapsed from the last dose of the agent, whichever is greater
  • Platelet count >= 20,000/mm^3 (may receive platelet transfusions)
  • Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)
  • Creatinine clearance or radioisotope glomerular filtration rate [GFR] >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
  • Age: Maximum serum creatinine (mg/dL)
  • 2 to < 6 years: 0.8 (male and female)
  • 6 to < 10 years: 1 (male and female)
  • 10 to < 13 years: 1.2 (male and female)
  • 13 to < 16 years: 1.5 (male); 1.4 (female)
  • >= 16 years: 1.7 (male); 1.4 (female)
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 225 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L
  • Serum albumin >= 2 g/dL
  • Left ventricular ejection fraction of >= 50% by echocardiogram
  • Regulatory Requirements
  • All patients and/or their parents or legal authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Who cannot join

  • AML associated with Down syndrome or t(15;17) is not eligible for study
  • Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy and for 2 months after the last dose of enasidenib. Abstinence is an acceptable method of birth control. It is not known if enasidenib is present in breast milk. Breastfeeding is not recommended during therapy or for at least 30 days after the last dose of enasidenib
  • Concomitant Medications:
  • Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. The use of corticosteroids to manage the side effect of IDH inhibitor-associated differentiation syndrome (IDH-DS), is permitted on study
  • Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
  • Anti-cancer agents: Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy; the use of hydroxyurea to manage the side effect of IDH-DS, is permitted on study)
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  • Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
  • Patients must be able to swallow intact tablets whole or use the alternate enasidenib formulation.
  • Patients with known hypersensitivity to any of the components of enasidenib are not eligible.
  • Patients with prior exposure to enasidenib or another IDH2 inhibitor are not eligible.
  • Patients taking the following drugs will be excluded from study entry unless these drugs are discontinued or patients are transferred to a medically acceptable alternative > 5 half-lives before the first dose of enasidenib.
  • Drugs with a narrow therapeutic range that are sensitive substrates of the following cytochrome P450 (CYP) enzymes: CYP2C8 (e.g. paclitaxel), 2C9 (e.g. phenytoin and warfarin), 2C19 (e.g. s-mephenytoin), 2D6 (e.g. thioridazine), and 1A2 (e.g. theophylline and tizanidine).
  • Breast cancer resistant protein (BCRP) transporter-sensitive substrate rosuvastatin
  • Patients with the following leukemia complications are not eligible for this trial:
  • No intrathecal chemotherapy is permitted on study. Prior to study enrollment, cerebrospinal fluid (CSF) evaluation is only required if there is a clinical suspicion for CNS leukemia. Clinical signs of CNS leukemia (such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome) are not eligible for this trial
  • Immediately life-threatening, severe complications of leukemia including uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation
  • Patients who have received a prior solid organ transplantation are not eligible
  • Infection: Patients who have an uncontrolled infection or patients with known human immunodeficiency virus (HIV) or active hepatitis B or C are not eligible
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Trial locations and contacts

28 sites in 2 countries.

28 sites in 2 countries

United States27 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado, 80218

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

  • Norton Children's Hospital

    Louisville, Kentucky, 40202

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Children's Hospital of San Antonio

    San Antonio, Texas, 78207

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

Canada1 site

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

Other trials in Canada

About this study

Official title: An Open-Label Feasibility Study to Assess the Safety and Pharmacokinetics of Enasidenib in Pediatric Patients With Relapsed/Refractory Acute Myeloid Leukemia (R/R-AML) With an Isocitrate Dehydrogenase-2 (IDH2) Mutation

This phase II trial studies the side effects of enasidenib and sees how well it works in treating pediatric patients with acute myeloid leukemia that has come back after treatment (relapsed) or has been difficult to treat with chemotherapy (refractory). Patients must also have a specific genetic change, also called a mutation, in a protein called IDH2. Enasidenib may stop the growth of cancer cells by blocking the mutated IDH2 protein, which is needed for leukemia cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety of treatment with enasidenib mesylate (enasidenib) administered at continuous daily oral dosing for a 28-day cycle up to 12 cycles in pediatric patients with IDH2-mutant relapsed/refractory (R/R)-acute myeloid leukemia (AML).

II. To characterize the plasma pharmacokinetic (PK) profile of enasidenib in pediatric patients with IDH2-mutant R/R-AML.

SECONDARY OBJECTIVES:

  1. To investigate the pharmacodynamic (PD) relationship of oncogenic metabolite 2-hydroxyglutarate (2-HG) to enasidenib treatment in pediatric patients with IDH2-mutant R/R-AML.

II. To describe the clinical activity of enasidenib in pediatric patients with IDH2-mutant R/R-AML.

IIa. Clinical activity will be defined as:

IIai. Overall response rate (ORR) using response criteria adapted from the AML International Working Group Criteria; IIaii. Composite complete remission rate (CCRR) defined as complete remission (CR) and complete remission with incomplete blood count recovery (CRi); IIaiii. Time to response (TTR); IIaiv. Time to complete remission (TTCR); IIav. Duration of response (DOR); IIavi. Duration of CR (DOCR); IIavii. Event-free survival (EFS) and overall survival (OS).

OUTLINE:

Patients receive enasidenib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and/or biopsy and collection of blood on study.

After completion of study treatment, patients are followed up at 30 days, then periodically up to 1 year.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Enasidenib, 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.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • EnasidenibDrug

    Also called AG 221, AG-221, AG221, CC-90007 Free Base

    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 NCT04203316
Study groupRoleWhat they receive
Treatment (enasidenib)ExperimentalPatients receive enasidenib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and/or biopsy and collection of blood on study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Enasidenib; Drug: Enasidenib Mesylate

What is being measured

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

  1. Incidence of dose limiting toxicities of enasidenib

    Frequencies (%) of patients with cycle 1 dose limiting toxicity stratified by dose level.

    Measured: Up to 28 days

  2. Area under the plasma concentration versus time curve of enasidenib

    A descriptive analysis of the area under the plasma concentration versus time curve of enasidenib during cycle 1 at pre-dose and 1, 2, 4, 6, and 24 hours post-dose including median, minimum and maximum stratified by dose level.

    Measured: Up to 2 days

  3. Total plasma clearance of enasidenib

    A descriptive analysis of the total plasma clearance of enasidenib during cycle 1 at pre-dose and 1, 2, 4, 6, and 24 hours post-dose including median, minimum and maximum by dose level.

    Measured: Up to 2 days

  4. Elimination half-life of enasidenib

    A descriptive analysis of the elimination half-life of enasidenib during cycle 1 at pre-dose and 1, 2, 4, 6, and 24 hours post-dose including median, minimum and maximum by dose level.

    Measured: Up to 2 days

  5. Maximum concentration of enasidenib

    A descriptive analysis of the maximum concentration of enasidenib during cycle 1 at pre-dose and 1, 2, 4, 6, and 24 hours post-dose including median, minimum and maximum by dose level.

    Measured: Up to 2 days

Secondary outcomes (9)

  1. Plasma 2-HG levels of enasidenib

    A descriptive analysis of the plasma 2-HG levels observed pre-dose at day 0, 28, and 84 of enasidenib including median, minimum and maximum by dose level.

    Measured: Up to 84 days

  2. Overall Response Rate of enasidenib

    Frequency (%) of patients with at least partial response by dose level.

    Measured: Up to 2 years

  3. Composite complete remission rate (complete remission [CR]/ CR with incomplete hematologic recovery [CRi])

    Will be reported in a table as frequency of response (%) for total overall response rate (ORR) stratified by dose level.

    Measured: Up to 2 years

  4. Time to response of enasidenib

    Median time to response with 95% confidence interval stratified by dose level.

    Measured: Up to 2 years

  5. Time to complete remission of enasidenib

    Median time to remission with 95% confidence interval stratified by dose level.

    Measured: Up to 2 years

  6. Duration of response of enasidenib

    Median duration of response with minimum and maximum stratified by dose level.

    Measured: Up to 2 years

  7. Duration of complete response of enasidenib

    Median duration of remission with minimum and maximum stratified by dose level.

    Measured: Up to 2 years

  8. Event-free survival of enasidenib

    Median time to event with 95% confidence interval stratified by dose level.

    Measured: Up to 2 years

  9. Overall survival of enasidenib

    Median time to death with 95% confidence interval stratified by dose level.

    Measured: Up to 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 posted18 Dec 2019
  2. Study start14 Aug 2023
  3. Primary completion30 Sep 2025
  4. Study completion3 Oct 2026 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04203316
Sponsor's protocol ID
ADVL18P1
Other IDs
NCI-2019-07902, ADVL18P1, ADVL18P1, U10CA180886
Status last verified
Jan 2026
First submitted
4 Dec 2019
Last updated
9 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by Children's Oncology Group at 28 sites in 2 countries.

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 49 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 9 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in United States, Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Incidence of dose limiting toxicities of enasidenib (time frame: Up to 28 days). The study lists 5 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 NCT04203316.

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 9 Jan 2026.

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