Discontinuation of Hypomethylating Agent and Venetoclax i... | NCT06511882

NCT06511882

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
AbbVie	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Consolidation and Discontinuation	Other	Consolidation: Patient will receive HMA (azacitidine or decitabine)/VEN (venetoclax) as part of standard of care treatment. At the conclusion of consolidation, if the results of the bone marrow biopsy are a negative Measurable Residual Disease (MRD), patient will continue to Discontinuation. Discontinuation: Monthly clinic visits with laboratory assessment and bone marrow biopsies (BMBs) with MRD testing every 3 months to closely monitor disease status. At any point of the study if molecular relapse (including MRD emergence), or morphologic relapse, therapy will be reinitiated. If only molecular relapse, HMA (azacitidine or decitabine)/VEN (venetoclax) will be reinitiated with the same monitoring schedule as before. If morphologic relapse, HMA (azacitidine or decitabine)/VEN (venetoclax) will be reinitiated for 2 cycles. If no response (NR), patient will be taken off Study.	Drug: Azacitidine Drug: Decitabine Drug: Venetoclax

Name	Type	Description	Arm Group Labels	Other Names
Azacitidine	Drug	Standard of Care Intravenous (IV) infusion	Consolidation and Discontinuation

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Rates of Complete Response (CR)/Complete Response with incomplete hematologic recovery (CRi)	Rates of CR/CRi at 18 months from the time of initial CR/CRi in patients who discontinue frontline HMA (azacitidine or decitabine)/VEN (venetoclax) after achieving Measurable Residual Disease (MRD) negativity by MFC within 12 months of starting therapy. The Null hypothesis (p0) will be tested against the alternative hypothesis (p1). Null hypothesis: p0 ≤ 50% will remain in CR/CRi at 18 months from the time of initial CR/CRi Alternative hypothesis: p1 ≥ 70% will remain in CR/CRi at 18 months from the time of initial CR/CRi	Up to 18 Months

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	Overall survival will be assessed in MRD-negative patients who discontinue HMA (azacitidine or decitabine)/VEN (venetoclx). Overall Survival (OS) is defined as the length of time from the start of treatment until death due to any cause.	Up to 36 Months
Rates to Re-Treatment

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Adults 18 years of age or older at the time of obtaining informed consent.
Diagnosed with Acute Myeloid Leukemia (AML) (non-M3) as defined by 2016 World Health Organization (WHO)
Eastern Cooperative Group (ECOG) performance status score ≤ 2
Currently on frontline therapy with HMA (azacitidine or decitabine)/VEN and achieved Complete Remission (CR)/Complete Remission with incomplete marrow recovery (CRi) with MRD negativity defined as < 0.1% by Multiparameter Flow Cytometry (MFC)
Within 12 months of starting HMA (azacitidine or decitabine)/VEN
Ineligible for or declined allogeneic hematopoietic cell transplantation (HCT)
Ability to understand and the willingness to sign a written informed consent document
Must agree to adhere to the study visit schedule and other protocol requirements
Patients must be able to provide adequate Bone Marrow (BM) aspirate and biopsy specimens for histopathological and Measurable Residual Disease analysis during the screening procedure

Exclusion Criteria:

Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of AML within 28 days, or 5 half-lives, at the start of the study. Only patients who are receiving frontline HMA (azacitidine or decitabine)/VEN are potentially eligible, but if they had received a course of hydroxyurea prior to achieving CR/CRi, this is allowed.
Any serious medical condition or uncontrolled current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or will place the subject at unacceptable risk if he/she participates in the study. Controlled infections or other medical conditions on long-term therapy is allowed.
Patients who harbored TP53 mutation at diagnosis
AML with extramedullary involvement including central nervous system (CNS) involvement, myeloid sarcoma, and leukemia cutis requiring directed therapy at the time of enrollment.
Patient is pregnant.

ID	Term
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms