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

Launched by M.D. ANDERSON CANCER CENTER · Dec 22, 2017

Keywords

ClinConnect Summary

This clinical trial is investigating how well two medications, azacitidine and enasidenib, work together to treat patients with a specific type of blood disorder known as IDH2-mutant myelodysplastic syndrome (MDS). MDS is a condition where the bone marrow doesn't produce enough healthy blood cells, and the presence of the IDH2 gene mutation can make it harder to treat. The goal of this study is to see if these medications can help stop the growth of cancer cells and improve patients' conditions.

To be eligible for the trial, participants must be diagnosed with MDS that includes certain criteria and have the IDH2 gene mutation confirmed by a lab test. They should also be able to understand and sign a consent form, and they should not have received certain prior treatments that might interfere with the study. Throughout the trial, participants will receive the study drugs and be monitored for their health and any side effects. This research is currently looking for participants of all ages and genders who meet these criteria. If you or someone you know is interested in this trial, it’s important to discuss it with a healthcare provider to understand the potential benefits and risks.

Gender

ALL

Eligibility 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