IDH2 Inhibition Using Enasidenib as Maintenance Therapy for IDH2-mutant Myeloid Neoplasms Following Allogeneic Stem Cell Transplantation

NCT03515512 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 18-022
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 4

Brief Summary

This research study is studying a targeted therapy drug as a possible treatment for IDH2 mutant acute myeloid leukemia or chronic myelomonocytic leukemia while undergoing hematopoietic stem cell transplantation. The drug involved in this study is:

• Enasidenib.

Conditions

Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia

Keywords

Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  The maximum tolerated dose of Enasidenib in this patient population. The Maximum Tolerated Dose (MTD) is defined as the highest dose level at which 0 or 1 of six patients experiences a dose-limiting toxicity (DLT). MTD is determined using a standard 3 + 3 dose escalation cohort, where 3 participants will be enrolled on the starting dose of 50 mg daily and if no DLT is experienced after a full 28-day cycle, 3 additional participants will be enrolled at the next dose level of 100mg daily. If during any dose level, 1 patient out of 3 develops a DLT, then 3 additional patients will be added to that dose level. If 2 out of the 3 patients placed on any dose level experience a DLT, the preceding dose is considered MTD. If 1 out of 6 participants has a DLT, the next higher dose level will commence accrual. If ≥ 2 of 6 patients have a DLT, then the preceding dose will be considered MTD.

  28 Days

• Number of participants with dose limiting toxicities (DLT)

  Dose limiting toxicities are adverse events that occur during the first 28-day cycle that are considered serious enough to prevent an increase in the Enasidenib dose level. Adverse events are graded and documented per Common Terminology Criteria for Adverse Events (CTCAE 4).

  28 days

Secondary Outcomes (6)

• The number of participants with Enasidenib related adverse events

  From the start of treatment until 30 days after the end of treatment, treatment may continue for up to 12 28-day cycles

• Cumulative incidence of acute GVHD

  Cycle 1 days 1, 8, and 15; day 1 of every subsequent cycle (cycles are 28-days), up to 100 days after the start of treatment

• Cumulative incidence of chronic GVHD

  Cycle 1 days 1, 8, and 15; Day 1 of cycles 2-12 (1 cycle is 28-days), up to 1 year of total follow-up

• Plasma and marrow 2-hydroxyglutarate levels

  Screening, cycle 1 days 8 and 15, day 1 of cycles 2 and 3, at the time of relapse, up to one year total follow-up

• IDH clonal evolution via whole genome sequencing

  Screening, cycle 1 days 8 and 15, day 1 of cycles 2 and 3, at the time of relapse, up to one year total follow-up

Study Arms (1)

Enasidenib

EXPERIMENTAL

Enasidenib will be administered orally once daily in 28-day cycles

Drug: Enasidenib

Interventions

Enasidenib DRUG

Enasidenib may help block the over production of IDH2, which when mutated, can overproduce metabolites and compounds that contribute to the growth of tumors and cancerous cells

Also known as: idhifa

Enasidenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed diagnosis of IDH2-mutant acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML).
• IDH2 mutations will include any IDH2 R140 or R172 alterations
• Eligibility and enrollment will be based on local IDH2 mutational testing performed at any center. The presence of an IDH2 mutation at the time of initial diagnosis or any other time thereafter is necessary and sufficient. The presence of an IDH2 mutation at time of enrollment is not necessary for the purposes of eligibility.
• Between the ages of 18 and 75 years
• Will undergo first allogeneic hematopoietic stem cell transplantation (HSCT) for their malignancy. Conditioning may have been either conventional myeloablative (MAC) or reduced intensity conditioning (RIC).
• HSCT Donor will be one of the following:
• /6 or 6/6 (HLA-A, B, DR) matched related donor
• /8 or 8/8 (HLA-A, B, DR, C) matched unrelated donor. Matching in the unrelated setting must be at the allele level.
• Haploidentical related donor, defined as ≥ 3/6 (HLA-A, B, DR) matched --≥ 4/6 (HLA-A, B, DR) umbilical cord blood (UCB). Matching in the UCB setting is at the antigen level. Recipients may receive either one or two UCB units. In the case of 2 UCB units, both units must have been at least 4/6 matched with the recipient.
• ECOG performance status ≤ 2
• Participants must have normal organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1000/µL without growth factor support (e.g. GCSF) in the previous 7 days
• Platelet count ≥ 50,000/µL without transfusional support in the previous 7 days
• AST (SGOT), ALT (SGPT) and Alkaline phosphatase \< 3x institutional upper limit of normal (ULN)
• Direct bilirubin \< 2.0 mg/dL

You may not qualify if:

• Prior allogeneic hematopoietic stem cell transplants.
• Evidence of relapsed/recurrent/residual disease as assessed by bone marrow aspirate and biopsy performed within 42 days prior to study entry.
• History of other malignancy(ies) unless
• the participant has been disease-free for at least 5 years and is deemed by the investigator to be at low risk of recurrence of that malignancy, or
• the only prior malignancy was cervical cancer in situ and/or basal cell or squamous cell carcinoma of the skin
• Known diagnosis of active hepatitis B or hepatitis C
• Current or history of congestive heart failure New York Heart Association (NHYA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (LVEF \< 50%, as measured by MUGA scan or echocardiogram)
• Current or history of ventricular or life-threatening arrhythmias or diagnosis of long-QT syndrome
• Systemic infection requiring IV antibiotic or antifungal or antiviral therapy within 7 days preceding the first dose of study drug, or other severe infection
• Known dysphagia, short-gut syndrome, gastroparesis, or other condition(s) that limits the ingestion or gastrointestinal absorption of drugs administered orally
• Uncontrolled hypertension (systolic blood pressure \[BP\] \> 180 mmHg or diastolic BP \> 100 mmHg)
• QTc interval (i.e., Friderica's correction \[QTcF\]) ≥ 450 ms or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) at screening
• Concomitant receipt of the following sensitive CYP substrate medications that have a narrow therapeutic range (unless the participant can be transferred to other medications at least 5 half-lives prior to the start of study treatment): paclitaxel and docetaxel (CYP2C8), phenytoin (CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline, and tizanidine (CYP1A2)
• Concomitant receipt of the breast cancer resistance protein (BCRP) transporter-sensitive substrate rosuvastain (unless the participant can be transferred to another medication at least 5 half-lives prior to the start of study treatment)
• Uncontrolled intercurrent illness that would limit compliance with study requirements.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Celgene: collaborator

Study Sites (4)

Johns Hopkins Cancer Center

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (2)

• Fathi AT, Kim HT, Soiffer RJ, Levis MJ, Li S, Kim AS, Mims AS, DeFilipp Z, El-Jawahri A, McAfee SL, Brunner AM, Narayan R, Knight LW, Kelley D, Bottoms AS, Perry LH, Wahl JL, Brock J, Breton E, Ho VT, Chen YB. Enasidenib as maintenance following allogeneic hematopoietic cell transplantation for IDH2-mutated myeloid malignancies. Blood Adv. 2022 Nov 22;6(22):5857-5865. doi: 10.1182/bloodadvances.2022008632.

  PMID: 36150050 DERIVED

• Shallis RM, Podoltsev NA. Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. Curr Opin Hematol. 2021 Mar 1;28(2):110-121. doi: 10.1097/MOH.0000000000000637.

  PMID: 33394722 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic

Interventions

enasidenib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Amir t Fathi, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 23, 2018
• First Posted: May 3, 2018
• Study Start: July 17, 2018
• Primary Completion: December 31, 2021
• Study Completion: February 13, 2023
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)