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

NCT04203316 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: ADVL18P1NCI-2019-07902U10CA180886
• Study Type: interventional
• Target: 1
• Locations: 2 countries
• Sites: 28

Brief 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). 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.

Conditions

Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (5)

• Incidence of dose limiting toxicities of enasidenib

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

  Up to 28 days

• 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.

  Up to 2 days

• 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.

  Up to 2 days

• 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.

  Up to 2 days

• 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.

  Up to 2 days

Secondary Outcomes (9)

• Plasma 2-HG levels of enasidenib

  Up to 84 days

• Overall Response Rate of enasidenib

  Up to 2 years

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

  Up to 2 years

• Time to response of enasidenib

  Up to 2 years

• Time to complete remission of enasidenib

  Up to 2 years

Study Arms (1)

Treatment (enasidenib)

EXPERIMENTAL

Patients 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.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Enasidenib; Drug: Enasidenib Mesylate

Interventions

Enasidenib DRUG

Given PO

Also known as: AG 221, AG-221, AG221, CC-90007 Free Base

Treatment (enasidenib)

Biospecimen Collection PROCEDURE

Undergo collection of blood

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (enasidenib)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (enasidenib)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (enasidenib)

Enasidenib Mesylate DRUG

Given PO

Also known as: 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, CC-90007, CC90007, Enasidenib Methanesulfonate, Idhifa

Treatment (enasidenib)

Eligibility Criteria

• Age: 24 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (28)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

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

Denver, Colorado, 80218, United States

Location

Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

UF Health Cancer Institute - Gainesville

Gainesville, Florida, 32610, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

Children's Hospital of San Antonio

San Antonio, Texas, 78207, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Specimen Handling; Biopsy; enasidenib; 2-Propanol; methanesulfonic acid

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Propanols; Alcohols; Organic Chemicals

Study Officials

• Sara Zarnegar-Lumley

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2019
• First Posted: December 18, 2019
• Study Start: August 14, 2023
• Primary Completion: September 30, 2025
• Study Completion (Estimated): October 3, 2026
• Last Updated: January 9, 2026

Record last verified: 2026-01

Locations

US (27); CA (1)