Oral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality (REMAIN1)

REMAIN1: Relapse Prevention With Maintenance Oral Azacitidine in Transplant Eligible Patients With Acute Myeloid Leukemia Not Proceeding to Transplant Due to Racial or Socioeconomic Disparities

Test feasibility of an oral maintenance strategy for transplant eligible AML patients in first CR who are medically underserved or have a disadvantage in the CDC SDOH domains

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Oral Azacitidine

Detailed Description

This is a non-randomized open-label single institution pilot study that will evaluate the feasibility, toxicity, and efficacy of maintenance oral azacitidine in medically transplant eligible non-FMS-like tyrosine kinase 3 (FLT3) mutated AML patients with a disadvantage in at least 1 of the 5 key Center for Disease Control and Prevention (CDC) defined social determinants of health (SDOH) domains that are preclusive to transplant at time of study enrollment, as identified either by the patient or a member of the healthcare team.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Massey IIT Research Operations; Phone Number: 804-628-6430; Email: masseyepd@vcu.edu

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University
      • Principal Investigator: Keri Maher, DO
      • Contact: Massey CTO Heme Team; Phone Number: 804-628-6430; Email: MasseyHemMlg@vcu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed non-Acute Promyelocytic (APL) FLT3 negative AML and have completed induction and consolidation as defined by the treating physician and must be in complete response (CR), Complete response with partial hematologic recovery (CRh), or Complete response with incomplete count recovery (CRi) at time of study enrollment
• For patients in CR1, AML disease phenotype must be one that is considered for allo HCT in CR1 (intermediate or high risk by European Leukemia Net (ELN), MRD+ CR, slow clearance of MRD) or any AML phenotype (aside from FLT3+ and APL) in CR2 and beyond
• Medically eligible for allogeneic hematopoietic cell transplant (allo HCT) as defined by either: treating physician discretion, transplant physician discretion, or hematopoietic cell transplantation-specific Comorbidity index (HCT-CI) index of 5 or less
• Age ≥ 18 years
• Enrollment must occur within 4 months of completion of therapy
• A patient or staff identified health disparity in 1 of the 5 Centers for Disease Control (CDC) defined social determinants of health (SDOH). This may include financial difficulties, lack of caregiver support, difficulties with medical literacy, rurality, appropriate access to health care, lack of an appropriate allogeneic hematopoietic cell transplant (allo HCT) donor, substance abuse
• Patient must have adequate organ function defined as: Creatinine clearance (by Cockroft-Gault formula) greater than or equal to 29 mL/min, total bilirubin and aspartate aminotransferase/ alanine transaminase (AST/ALT) ≤ to institutional 2x upper limit of normal (except Gilbert's syndrome, which may enroll if < 2x patient's baseline total bilirubin)
• Eastern Cooperative Oncology Group (ECOG) 0,1,2,3
• Ability to take oral medications
• No history of malabsorption syndrome which, in the investigator's opinion, may inhibit absorption of oral medications
• Women of childbearing potential must consent to effective contraception during study treatment and at least 6 months following the last dose. Women who are breastfeeding are also excluded
• Male patients must consent to effective contraception during study and at least 3 months after last dose
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria A patient who meets any of the following exclusion criteria is ineligible to participate in the study.

• FMS-like tyrosine kinase 3 (FLT3 ITD) or tyrosine kinase domain (TKD) mutation
• Uncontrolled central nervous system (CNS) involvement
• History of hypersensitivity or allergic reaction to azacitidine or its components
• Stem cell transplant within previous 3 months prior to initiation of study therapy
• Uncontrolled intercurrent illness or infection
• History of prior therapy with oral azacitidine
• Female patients who are pregnant or intend to donate eggs during the study or for 6 months after receiving their last dose of study drug
• Male patients who intend to donate sperm during the course of this study or for 3 months after last dose
• Other malignancy for which the patient is currently receiving therapy (except excisable skin cancer)
• Medical, psychological, or social condition that, in the opinion of the investigator, may increase the participant's risk or limit the participant's adherence with study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Azacitidine; Starting dose is oral azacitidine 300 mg orally once daily with or without food days 1-14 in a 28-day cycle	Drug: Oral Azacitidine; Oral Azacitidine, 300mg PO Daily during days 1-14 of a 28 day cycle for up to 6 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of completion of at least 4 cycles an oral maintenance strategy for transplant eligible AML patients in CR who are medically underserved or have a disadvantage in the CDC SDOH domains	The number of participants that complete at least four cycles of protocol therapy	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Number of participants alive at relapse, completion of treatment or removal from study.	3 months, and up to 2 years
Leukemia Free Survival (LFS) 3 months after beginning of treatment and at relapse, completion of treatment or removal from study	Number of participants still in remission 3 months after beginning of treatment and at relapse, completion of treatment or removal from study	3 months, and up to 2 years
Measure rates of measurable residual disease (MRD) negativity	The number of participants that have negative measurable residual disease (MRD) at 3 months after beginning of treatment, and completion of treatment. MRD will be measured by flow cytometry and by pathologic complete response (PCR) based molecular assay if/when target gene is available on diagnostic specimen.	3 months, and up to 2 years
Assess whether such an approach may provide an effective bridge to curative intent allogeneic hematopoietic stem cell transplant (alloHCT)	Number of patients who successfully move on to receive an allogeneic hematopoietic stem cell transplant (alloHCT).	Up to 2 years

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Keri Maher, DO, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2029

Study Registration Dates

• First Submitted: April 12, 2024
• First Submitted That Met QC Criteria: April 12, 2024
• First Posted (Actual): April 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine
• Other Study ID Numbers: MCC-23-20817; HM20029540 (Other Identifier: Virginia Commonwealth University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share individual patient data. Datasets are available on reasonable request to the author.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No