A Study to Assess Safety and Tolerability of CC-486 (ONUREG®, Oral Azacitidine) in Combination Therapy in Participants With Acute Myeloid Leukemia (AML)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of CC-486 (ONUREG®) in combination with venetoclax in relapsed and/or refractory Acute Myeloid Leukemia (AML) and newly diagnosed AML.

Official Title
-----------------
A Phase 1B, Open-label, Global, Multicenter, Dose Determination Study to Evaluate Safety, Tolerability, and Preliminary Efficacy of CC-486 (ONUREG®) in Combination Therapy in Subjects With Acute Myeloid Leukemia (AML)

Conditions
-----------------
Leukemia, Myeloid, Acute

Intervention / Treatment
-----------------
* Drug: CC-486
* Drug: Venetoclax


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmation of the following for Acute Myeloid Leukemia (AML) Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. ECOG 3 is allowed if participants are 18 to 74 years old with comorbidities Agree to serial bone marrow aspirate/biopsies Exclusion Criteria: Suspected or proven to have acute promyelocytic leukemia based on morphology, immunophenotype, molecular assay, or karyotype Received prior hypomethylating agent (HMA) therapy for myelodysplastic syndromes/Chronic myelomonocytic leukemia then develop AML within 4 months of discontinuing the HMA therapy Prior history of malignancy unless the participant has been free of the disease for ≥ 1 year prior to the start of study treatment Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CC-486 in combination with Venetoclax<br> | Drug: CC-486<br>* Specified dose on specified days<br>* Other names: ONUREG®, oral azacitidine;Drug: Venetoclax<br>* Specified dose on specified days<br>* Other names: VENCLEXTA®, VENCLYXTO®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) |  | Up to 42 days after first dose | 
| Incidence of type of adverse events (AEs) |  | From informed consent form (ICF) signature to 28 days after last dose of study drug | 
| Incidence of frequency of AEs |  | From informed consent form (ICF) signature to 28 days after last dose of study drug | 
| Incidence of severity of AEs |  | From informed consent form (ICF) signature to 28 days after last dose of study drug | 
| Incidence of relationship of AEs to study treatment |  | From informed consent form (ICF) signature to 28 days after last dose of study drug | 
| Incidence of clinically significant changes in clinical laboratory results: Hematology tests |  | From informed consent form (ICF) signature to 28 days after last dose of study drug | 
| Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests |  | From informed consent form (ICF) signature to 28 days after last dose of study drug | 
| Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests |  | From informed consent form (ICF) signature to 28 days after last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete remission (CR)/complete remission with partial hematologic recovery (CRh) |  | Up to approximately 12 months | 
| Overall Response Rate (ORR) |  | Up to approximately 12 months | 
| Minimal Residual Disease (MRD) Response Rate |  | Up to approximately 12 months | 
| MRD Conversion Rate |  | Up to approximately 12 months | 
| Rate of complete remission (CR)/complete remission with incomplete recovery of blood counts (CRi) |  | Up to approximately 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
venetoclax, Acute Myeloid Leukemia, CC-486, Onureg, oral azacitidine, Venclexta, Venclyxto