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

• Status: Active, not recruiting
• Trial end date: 2023-02-28
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborators: Celgene; National Cancer Institute (NCI)
• Treatments: Azacitidine

Criteria

Inclusion Criteria:

• 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): Subject must be hypomethylating agent naive (i.e. prior azacitidine, decitabine, SGI-110 is exclusionary). Receipt of other MDS-directed therapy such as lenalidomide is allowed

• (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

Exclusion Criteria:

• 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