A Phase I/II Trial to Assess the Efficacy and Toxicity of ASTX727 (Oral Decitabine/Cedazuridine) for the Treatment of Hematological Neoplasms After Allogeneic Stem Cell Transplantation

NCT06297629 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-0636NCI-2024-01689
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if ASTX727 given alone or in combination with donor lymphocyte infusion (DLI) can help to control certain types of hematological neoplasms (blood-based cancers) after a stem cell transplant.

Conditions

Allogeneic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (2)

Group 1

EXPERIMENTAL

If participants test positive for minimal residual disease (MRD), participants will be enrolled in Group 1. MRD refers to small numbers of cancer cells that remain in the body during or after treatment. Participants in this group will receive ASTX727 and DLI. If participants are enrolled in Group 1, the participant will take ASTX727 on Days 1-4 of each cycle.

Drug: ASTX727; Drug: Donor Lymphocyte Infusion

Group 2

EXPERIMENTAL

If participants do not test positive for MRD, you will be enrolled in Group 2. Participants in this group will only receive ASTX727. If participants are enrolled in Group 2, the participant will take ASTX727 on Days 1-3 of each cycle.

Drug: ASTX727

Interventions

ASTX727 DRUG

Given by PO

Also known as: Inqovi

Group 1; Group 2

Donor Lymphocyte Infusion DRUG

Given by Infusion

Also known as: DLI

Group 1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of AML and MDS according to World Health Organization (WHO) classification that underwent first or second allogeneic HSCT with either peripheral blood or bone marrow as the source of the hematopoietic stem cells.
• Age 18 to 75 years old.
• High risk patients defined per cohorts as below:
• Cohort #1: AML and MDS patients in morphological remission with persistence or reappearance of MRD by flow cytometry or molecular after allogeneic stem cell transplantation who are beyond day 100 after allogeneic stem cell transplantation.
• When MRD is detected by flow cytometry, disease level at or above the sensitivity level of the test will be required.
• MRD level at or above 0.1%.
• When MRD is detected by molecular testing, disease level at or above the sensitivity level of the test will be required.
• The limit of detection is 0.01%
• Cohort #2: High risk AML and MDS patients who are in complete remission morphologically with no evidence of minimal residual disease by flow cytometry or cytogenetic or molecular testing within 100 days after allogeneic stem cell transplantation.
• MDS patients:
• Moderate-high, high or very high-risk groups by International Prognostic Scoring System-Molecular (IPSS-M) classification if classification is available (58).
• TP53 with biallelic mutations(49).
• Therapy-related MDS(50).
• Presence of mutation ASXL1, SRSF2, DNMT3A, RUNX1, U2AF1, TP53, EZH2, STAG2, CBL, NRAS, BCOR ((49, 51-54))
• Bone marrow blast count 10% or higher prior to allogeneic stem cell transplantation.

You may not qualify if:

• Use of any anti-leukemic agents after MRD is documented (note that the use of these anti-leukemic agents given as post-transplant maintenance therapy is allowed in this study, e.g., subcutaneous or oral 5-Azacytidine or FLT3 inhibitors for maintenance, for cohort #1 patients. However, all those agents will be discontinued once the patient enrolls into the current trial for cohort #1.
• Use of any of the following after transplantation and prior to starting study therapy for cohort #2. Anti-leukemic agents given as post-transplant maintenance therapy (e.g., subcutaneous or oral 5-Azacytidine or FLT3 inhibitors for maintenance).
• Overall grade II-IV acute GVHD. However, upon complete resolution of acute GVHD-related symptoms, patients are eligible for enrollment if they are on prednisone 0.5 mg/kg daily dose or lower, tacrolimus, sirolimus and ruxolitinib.
• Chronic GvHD, moderate or severe by NIH criteria.
• Active uncontrolled systemic fungal, bacterial or viral infection. However, patients receiving anti-microbial agents including antibiotics, antiviral and antifungal therapies are allowed if hemodynamically stable.
• Symptomatic or uncontrolled arrhythmias.
• Significant active cardiac disease within the previous 6 months, including:
• New York Hear Association (NYHA) class III or IV congestive heart failure;
• Unstable angina or angina requiring surgical or medical intervention, and/or; Myocardial infarction.
• Known active viral infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
• Patients with known active hepatitis B virus (HBV) infection will be excluded because of potential effects on immune function and/or drug interactions. However, if a patient has HBV history with an undetectable HBV load by polymerase chain reaction (PCR), no liver-related.
• complications, and is on definitive HBV therapy that is not contraindicated on this study, then he/she would be eligible for study.
• Patients with known active hepatitis C virus (HCV) infection will be excluded because of potential effects on immune function and/or drug interactions. However, if a patient with a history of HCV infection has received definitive therapy (and is now HCV viral load negative), or if a patient has a reactive HCV antibody test but has an undetectable viral load by PCR, then he/she would be eligible.
• Patients with known active HIV infection will be excluded out of concern for the drug-drug interaction with venetoclax and highly active antiretroviral therapy (HAART).
• \- Prior history of solid tumors other than AML and MDS, unless the subject has been free of the disease for \>/= 1 year. However, subjects with the following history/concurrent conditions are allowed:

Sponsors & Collaborators

• Astex Pharmaceuticals, Inc.: collaborator
• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

decitabine and cedazuridine drug combination

Study Officials

• Betul Oran, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2024
• First Posted: March 7, 2024
• Study Start: July 1, 2024
• Primary Completion: July 11, 2024
• Study Completion: July 11, 2024
• Last Updated: February 24, 2026

Record last verified: 2025-04

Locations

US (1)