Enasidenib and Azacitidine in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia and IDH2 Gene Mutation

NCT03683433 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2018-0499NCI-2018-01919
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well enasidenib and azacitidine work in treating patients with IDH2 gene mutation and acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory). Enasidenib and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Acute Bilineal Leukemia; Acute Biphenotypic Leukemia; Chronic Myelomonocytic Leukemia; IDH2 Gene Mutation; Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  The study will estimate the ORR for the combination treatment, along with the Bayesian 95% credible interval. ORR will be defined as the proportion of patients who had CR (complete remission), CRh (complete remission with incomplete hematologic recovery), CRi (complete remission with incomplete count recovery), PR (partial response), and/or marrow clearance of blasts (MLFS).

  Up to 5 years

Secondary Outcomes (5)

• Event-free survival

  Up to 5 years

• Overall survival (OS)

  Up to 5 years

• Disease-free survival (DFS)

  Up to 5 years

• Duration of response

  Up to 5 years

• Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  Up to 5 years

Other Outcomes (3)

• Minimal residual disease (MRD)

  Up to 5 years

• Association of biomarkers to overall response

  Up to 5 years

• Change in markers over time

  Baseline up to 5 years

Study Arms (1)

Treatment (azacitidine, enasidenib mesylate)

EXPERIMENTAL

Patients receive azacitidine SC or IV over 30 minutes on days 1-7 and enasidenib mesylate PO QD beginning on day 1. Cycles repeat every 4-6 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine; Drug: Enasidenib Mesylate

Interventions

Azacitidine DRUG

Given SC or IV

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

Treatment (azacitidine, enasidenib mesylate)

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, Enasidenib Methanesulfonate, Idhifa

Treatment (azacitidine, enasidenib mesylate)

Eligibility Criteria

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

You may qualify if:

• Patients with AML or biphenotypic or bilineage leukemia (including a myeloid component) who have failed prior therapy. Patients with isolated extramedullary AML are eligible. The World Health Organization (WHO) classification will be used for AML
• Elderly (\> 60 years old) patients with newly diagnosed AML not eligible for intensive chemotherapy are also eligible
• AML patients with prior history of myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) regardless of prior therapy received, are eligible at the time of diagnosis of AML
• Subjects must have documented IDH2 gene mutation
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 3
• Adequate renal function including creatinine \< 2 unless related to the disease
• Total bilirubin \< 2 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \< 3 x ULN unless considered due to leukemic involvement
• Provision of written informed consent
• Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the principal investigator (PI). Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted
• Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment
• Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment

You may not qualify if:

• Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British \[FAB\] class M3-AML)
• Active and uncontrolled comorbidities including active uncontrolled infection, uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure New York Heart Association (NYHA) class III/IV, clinically significant and uncontrolled arrhythmia as judged by the treating physician
• Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator
• Pregnant or breastfeeding

Sponsors & Collaborators

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

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

• Venugopal S, Takahashi K, Daver N, Maiti A, Borthakur G, Loghavi S, Short NJ, Ohanian M, Masarova L, Issa G, Wang X, Carlos BR, Yilmaz M, Kadia T, Andreeff M, Ravandi F, Konopleva M, Kantarjian HM, DiNardo CD. Efficacy and safety of enasidenib and azacitidine combination in patients with IDH2 mutated acute myeloid leukemia and not eligible for intensive chemotherapy. Blood Cancer J. 2022 Jan 25;12(1):10. doi: 10.1038/s41408-021-00604-2.

  PMID: 35078972 DERIVED

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Azacitidine; 2-Propanol; methanesulfonic acid; enasidenib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Courtney DiNardo

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Courtney DiNardo

CONTACT

713-794-1141; cdinardo@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: September 19, 2018
• First Posted: September 25, 2018
• Study Start: September 18, 2018
• Primary Completion (Estimated): September 20, 2027
• Study Completion (Estimated): September 20, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (1)