Azacitidine and Enasidenib in Treating Patients With IDH2-Mutant Myelodysplastic Syndrome

NCT03383575 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: 2016-0981NCI-2018-00987P30CA016672
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial studies the side effects and how well azacitidine and enasidenib work in treating patients with IDH2-mutant myelodysplastic syndrome. Azacitidine and enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Chronic Myelomonocytic Leukemia; IDH2 Gene Mutation; Myelodysplastic Syndrome With Excess Blasts; Recurrent High Risk Myelodysplastic Syndrome; Refractory High Risk Myelodysplastic Syndrome; Acute Myeloid Leukemia; Blasts 20-30 Percent of Bone Marrow Nucleated Cells

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Will use the Bayesian method by Thall, Simon and Estey for toxicity monitoring. For purpose of toxicity monitoring, toxicity is defined as any grade 3 or higher treatment related-toxicities by Common Terminology Criteria for Adverse Events criteria.

  Up to 3 years

• Overall response rate

  Defined as complete response (CR), partial response, and marrow CR assessed by International Working Group criteria. Will be estimated along with the 90% credible interval.

  Up to 3 years

Secondary Outcomes (5)

• Event-free survival (EFS)

  Up to 3 years

• Overall survival (OS)

  Up to 3 years

• Anti-tumor activity

  Up to 3 years

• Pharmadynamics (PDn) markers

  Up to 3 years

• Drug exposure levels

  Up to 3 years

Other Outcomes (1)

• Biomarkers analysis

  Up to 3 years

Study Arms (2)

Arm I (enasidenib, azacitidine)

EXPERIMENTAL

Patients who are HMA-naive receive enasidenib PO QD on days 1-28 and azacitidine IV over 30-60 minutes or SC on days 1-7. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine; Drug: Enasidenib; Other: Quality-of-Life Assessment

Arm II (enasidenib)

EXPERIMENTAL

Patients relapsed and/or refractory to HMA therapy receive enasidenib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Enasidenib; Other: Quality-of-Life Assessment

Interventions

Enasidenib DRUG

Given PO

Also known as: AG-221, CC-90007

Arm I (enasidenib, azacitidine); Arm II (enasidenib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (enasidenib, azacitidine); Arm II (enasidenib)

Azacitidine DRUG

Given IV or SC

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Arm I (enasidenib, azacitidine)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed, informed consent must be obtained prior to any study specific procedures
• Subjects with a histologically confirmed diagnosis of MDS, including both MDS and refractory anemia with excess blasts in transformation (RAEB-T) (acute myeloid leukemia \[AML\] with 20-30% blasts and multilineage dysplasia by French-American-British \[FAB\] criteria) by World Health Organization (WHO), and chronic myelomonocytic leukemia (CMML) are eligible
• Subjects must have an IDH2 gene mutation (IDH2-R140 or R172) as determined by local laboratory result
• (Arm A only): Subjects with high-risk MDS (i.e. International Prostate Symptom Score \[IPSS\] intermediate-2 or high-risk; or revised \[R\]-IPSS high or very-high risk). Patients with intermediate-1 risk by IPSS or intermediate risk by R-IPSS with high-risk molecular features including TP53, ASXL1, EZH2, and/or RUNX1 mutations are also eligible
• (Arm B only): Subject must be relapsed or refractory to prior hypomethylating agent therapy, defined as prior receipt of 6 cycles of HMA therapy with failure to attain a response, or relapse after prior response to HMA therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Serum bilirubin =\< 2 x the upper limit of normal (ULN) (except for patients with Gilbert's disease)
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =\< 3 x the laboratory ULN
• Serum creatinine =\< 2 x the ULN
• Able to understand and voluntarily sign a written informed consent, and willing and able to comply with protocol requirements
• Resolution of all clinically significant treatment-related, non-hematological toxicities, except alopecia, from any previous cancer therapy to =\< grade 1 prior to the first dose of study treatment
• Female patients of childbearing potential must have a negative serum or urine pregnancy test within 7 days of the first dose of study drug and agree to use dual methods of contraception during the study and for a minimum of 3 months following the last dose of study drug. Post-menopausal females (\> 45 years old and without menses for \> 1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for a minimum of 3 months following the last dose of study drug if sexually active with a female of childbearing potential

You may not qualify if:

• Any prior or coexisting medical condition that in the investigator's judgment will substantially increase the risk associated with the subject's participation in the study
• Subject has received a prior targeted IDH2 inhibitor
• Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
• Active uncontrolled infection at study enrollment including known diagnosis of human immunodeficiency virus or chronic active hepatitis B or C infection
• Clinically significant gastrointestinal conditions or disorders that may interfere with study drug absorption, including prior gastrectomy
• Patients with known active central nervous system (CNS) disease, including leptomeningeal involvement
• Impaired cardiac function, uncontrolled cardiac arrhythmia, or clinically significant cardiac disease including the following: a) New York Heart Association grade III or IV congestive heart failure, b) myocardial infarction within the last 6 months
• Subjects with a corrected QT (QTc) \> 480 ms (QTc \> 510 msec for subjects with a bundle branch block at baseline
• Nursing or pregnant women
• Subjects with known hypersensitivity to study drugs or their excipients

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Celgene: collaborator

Study Sites (3)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

ACTIVE NOT RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

ACTIVE NOT RECRUITING

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

• DiNardo CD, Venugopal S, Lachowiez C, Takahashi K, Loghavi S, Montalban-Bravo G, Wang X, Carraway H, Sekeres M, Sukkur A, Hammond D, Chien K, Maiti A, Masarova L, Sasaki K, Alvarado Y, Kadia T, Short NJ, Daver N, Borthakur G, Ravandi F, Kantarjian HM, Patel B, Dezern A, Roboz G, Garcia-Manero G. Targeted therapy with the mutant IDH2 inhibitor enasidenib for high-risk IDH2-mutant myelodysplastic syndrome. Blood Adv. 2023 Jun 13;7(11):2378-2387. doi: 10.1182/bloodadvances.2022008378.

  PMID: 35973199 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Anemia, Refractory, with Excess of Blasts

Interventions

Azacitidine; 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; Anemia, Refractory; Anemia; Myelodysplastic Syndromes

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Courtney DiNardo

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Courtney DiNardo, MD

CONTACT

713-794-1141; cdinardo@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2017
• First Posted: December 26, 2017
• Study Start: January 17, 2018
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (3)