Enasidenib and Azacitidine in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia and IDH2 Gene Mutation
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03683433|
Recruitment Status : Recruiting
First Posted : September 25, 2018
Last Update Posted : August 16, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Bilineal Leukemia Acute Biphenotypic Leukemia Chronic Myelomonocytic Leukemia IDH2 Gene Mutation Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia||Drug: Azacitidine Drug: Enasidenib Mesylate||Phase 2|
I. To determine the clinical activity of enasidenib mesylate (AG221, IDHIFA) in combination with azacitidine (AZA) for patients with relapsed/refractory acute myeloid leukemia is measured by overall response rate (ORR).
I. To determine duration of response, event-free survival (EFS), and overall survival (OS).
II. To determine the safety of enasidenib in combination with azacitidine in patients with relapsed/refractory acute myeloid leukemia (AML).
I. To evaluate occurrence of minimal residual disease (MRD) negative status by IDH2 mutation analysis and flow cytometry.
II. To investigate possible relationships between baseline protein and gene expression signatures and mutation profile and clinical response to the combination.
III. To evaluate the incidence and characteristics of IDH-inhibitor related differentiation syndrome (IDH-DS) with combination therapy.
Patients receive azacitidine subcutaneously (SC) or intravenously (IV) over 30 minutes on days 1-7 and enasidenib mesylate orally (PO) once daily (QD) beginning on day 1. Cycles repeat every 4-6 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of the Targeted Mutant IDH2 Inhibitor Enasidenib in Combination With Azacitidine for Relapsed/Refractory AML|
|Actual Study Start Date :||September 18, 2018|
|Estimated Primary Completion Date :||September 20, 2021|
|Estimated Study Completion Date :||September 20, 2021|
Experimental: Treatment (azacitidine, enasidenib mesylate)
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.
Given SC or IV
Drug: Enasidenib Mesylate
- Overall response rate (ORR) [ Time Frame: Up to 5 years ]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).
- Event-free survival [ Time Frame: Up to 5 years ]Kaplan-Meier method will be used to estimate the probabilities of event-free survival.
- Overall survival (OS) [ Time Frame: Up to 5 years ]Kaplan-Meier method will be used to estimate the probabilities of overall survival.
- Disease-free survival (DFS) [ Time Frame: Up to 5 years ]Log-rank tests will be used to compare among subgroups of patients in terms of DFS or OS.
- Duration of response [ Time Frame: Up to 5 years ]Log-rank tests will be used.
- Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ]
- Minimal residual disease (MRD) [ Time Frame: Up to 5 years ]MRD negative status and exploratory biomarkers will be summarized graphically and with descriptive statistics.
- Association of biomarkers to overall response [ Time Frame: Up to 5 years ]Association between molecular and cellular markers and overall response and/or resistance assessed through logistic regression analyses.
- Change in markers over time [ Time Frame: Baseline up to 5 years ]Paired t-test or Wilcoxon signed rank test will be used to assess the marker change over time.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03683433
|Contact: Courtney DiNardofirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Courtney DiNardo 713-794-1141|
|Principal Investigator: Courtney DiNardo|
|Principal Investigator:||Courtney DiNardo||M.D. Anderson Cancer Center|