A Phase Ia/Ib Open-label, Multiple Dose, Study to Determine the Recommended Dose, Evaluate PKs, PDs, Safety, and Activity of Venetoclax in Combination With Oral Decitabine/Cedazuridine (ASTX727) in Pediatric Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)

NCT06191978 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2023-0661NCI-2023-10826
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

To find a recommended dose of ASTX727 (cedazuridine/decitabine) in combination with venetoclax for pediatric patients with relapsed AML.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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 (1)

ASTX727/venetoclax

EXPERIMENTAL

On Days 1-5 of Cycle 1, you will take ASTX727 by mouth with a glass of water. Participants must fast (not eat or drink anything but water, black coffee, or tea) for at least 2 hours before and for 2 hours after taking ASTX727. For 4 hours before dosing and 4 hours after dosing, participants should not take antacids or any other medicine that can change the amount of acid in your stomach. Days 1-21 or 1-28 depending on dose level, of all cycles beginning with Cycle 2. The study doctor will tell participants which of these schedules participants will follow. Venetoclax should be taken with water and a meal at around the same time each day.

Drug: ASTX727; Drug: Venetoclax

Interventions

ASTX727 DRUG

Given by PO

Also known as: Inqovi

ASTX727/venetoclax

Venetoclax DRUG

Given by PO

Also known as: ABT-199, GDC-0199

ASTX727/venetoclax

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Pediatric Participants with Relapsed/refractory AML by WHO criteria.
• Participants must have ≥ 5% blasts in the bone marrow as assessed by morphology or flow cytometry. However, if an adequate bone marrow sample cannot be obtained, participants may be enrolled if there is unequivocal evidence of leukemia with ≥ 5% blasts in the peripheral blood or an AML defining genetic abnormality as specified by the WHO 2022 criteria.
• Performance status: Lansky ≥ 50 for participants who are ≤ 16 years old and Karnofsky ≥ 50% for participants who are \> 16 years old.
• Age ≥2 years of age and ≤18 years of age
• Able to swallow pills
• The following baseline laboratory data:
• Total serum bilirubin ≤1.5 x upper limit of normal (ULN) for age, unless the increased value is likely attributed to disease involvement. Participants with known Gilbert's syndrome may have a total bilirubin up to ≤5 x ULN for age.
• Creatinine clearance (Schwartz-Formula) or radioisotope GFR ≥ 60ml/min/1.73 m2 or a serum creatinine based on age/sex as follows:
• Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤3 x ULN; ≤5 x ULN in case of suspected leukemic liver involvement.
• Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 6 months following the last dose of study drug. Effective methods of birth control include:
• i. Birth control pills, skin patches, shots, implants (placed under the skin by a health care provider) ii. Intrauterine devices (IUDs) iii. Condom or occlusive cap (diaphragm or cervical/vault caps) used with Spermicide iv. Abstinence e. Males, need to inform the doctor right away if the partner becomes pregnant or suspects pregnancy. While in this study and for 3 months after the last treatment the patient should not donate sperm for the purposes of reproduction. He will need to use a condom while in this study and for 3 months after the last treatment.
• At least one parents or LAR must provide signature of informed consent and there must be documentation of assent by the subject, as age appropriate, before completing any study-related procedures.

You may not qualify if:

• Concomitant other anti-cancer therapy and/or participation in any other investigational clinical trials except for hydroxyurea. Concurrent hydroxyurea use should be limited to the first 2 cycles of therapy only.
• History of another primary invasive malignancy that has not been definitively treated and is in remission. Participants with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses).
• Presence of clinically significant uncontrolled central nervous system (CNS) pathology such as epilepsy, childhood seizure, paresis, aphasia, stroke, severe brain injuries, organic brain syndrome, or psychosis.
• Evidence of active cerebral/meningeal disease. Participants may have history of CNS leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of consent with at least 2 consecutive spinal fluid negative assessments for residual leukemia and negative imaging (imaging required only if previously showing evidence of CNS leukemia not otherwise documented by spinal fluid assessment).
• Participants with uncontrolled, active infections (viral, bacterial, or fungal) or other disease expected to interfere with the ability of the PI to assess the efficacy of the study drug. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable.
• Known active hepatitis B (eg, HBsAg reactive), or hepatitis C (eg, HCV RNA \[qualitative\] is detected), or chronic hepatitis B or C infection or human immunodeficiency virus (HIV) infection in medical history (historical results within 6 months prior to informed consent is acceptable), with the following exceptions:
• a. Those with a history of hepatitis with a negative polymerase chain reaction (either qualitative or quantitative) OR have documentation of stable disease with aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase \<2.0×upper limit of normal (ULN) may be eligible for this study.
• b) Subjects with history of HIV who have an undetectable viral load for the prior 3 months, and who agree to maintain antiviral therapy, may be eligible for the study.
• Liver cirrhosis or other serious active liver disease or with suspected active alcohol abuse.
• Exclude participants with active GVHD and those on immunosuppressive drugs for treatment of GVHD. Require that participants be off calcineurin inhibitors for at least 4 weeks to be eligible.
• Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exception:
• a. To reduce the circulating blast count or palliation: intravenous cytarabine, steroids or hydroxyurea. No washout necessary for these agents.
• Females who are pregnant or lactating.
• Male or female subjects of childbearing potential, unwilling to use an approved, effective means of contraception.
• Other severe, uncontrolled acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the Investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the participant inappropriate for enrollment into this study.

Sponsors & Collaborators

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

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

decitabine and cedazuridine drug combination; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Amber Gibson, DO

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amber Gibson, DO

CONTACT

(713) 745-8177; algibson2@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2023
• First Posted: January 5, 2024
• Study Start: March 7, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

US (1)