Phase1b/2 Trial Of AZA + APG1252 In Patients With High-Risk AML

This is a phase Ib/II study that aims to investigate the safety, tolerability and explore the efficacy of BCL- XL inhibition in participants with high-risk AML.

Study Overview

• Status: Recruiting
• Conditions: AML
• Intervention / Treatment: Drug: Azacitidine; Drug: APG1252

Detailed Description

Primary Objectives:

Phase Ib: To evaluate the safety, tolerability, and maximum tolerated dose of APG1252 in combination with Azacitidine in patients with relapsed or refractory (R/R) high-risk Acute Myeloid Leukemia (AML)

Phase II: To evaluate the initial efficacy information in terms of ORR (CR/CRi/MLFS).

Secondary Objectives:

• [Phase Ib] To evaluate response (complete response [CR] including complete response without blood count recovery [CRi] or marrow leukemia free state [MLFS]) of APG1252 in combination with Azacitidine
• [Phase Ib and Phase II] To evaluate the event free survival of APG1252 in combination with Azacitidine in patients with high-risk AML
• [Phase Ib and Phase II] To assess the time to response, response duration, relapse-free survival, and overall survival (OS) in patients with AML treated with APG1252 in combination with Azacitidine

Although the clinical benefit of this drug has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit, and thus the patient will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Tapan Kadia, MD; Phone Number: (713) 563-3534; Email: tkadia@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • UT MD Anderson
      • Principal Investigator: Tapan Kadia, MD
      • Contact: Tapan Kadia, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Part I, Lead-in phase and Part II, Cohort A:

   Patients with relapsed and/or refractory AML Patients with high-risk MDS/AML who have had prior therapy will also be included

2. Part II, Cohort B

   Patients with untreated, newly diagnosed AML of the following subtypes:

   • AML-M6 or AML-M7 by FAB or having erythroid or megakaryocytic differentiation by WHO 2022 classification
   • High-risk MDS/AML with erythroid differentiation and no prior therapy
   • AML with MECOM rearrangement, including, but not limited to t(3;3), inv(3q), confirmed by conventional karyotype or FISH for MECOM rearrangement.
3. Age >/= 18 years. Because no dosing or adverse event data are currently available on the use of APG1252 in combination with AZA in patients <18 years of age, children are not included in this study at this time.

4. Adequate organ function as defined below:

   Liver function (bilirubin < 2mg/dL, AST and ALT <3 x ULN - or ≤5 x ULN if related to leukemic involvement) Kidney function (estimated creatinine clearance > 50 mL/min). Known cardiac ejection fraction of > or = 45% within the past 3 months

5. ECOG performance status of ≤ 2.
6. A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
7. Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol.

The effects of APG1252 on the developing human fetus are unknown. For this reason and because BCL-2/BCL-XL inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:

• Postmenopausal (no menses in greater than or equal to 12 consecutive months).
• History of hysterectomy or bilateral salpingo-oophorectomy.
• Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
• History of bilateral tubal ligation or another surgical sterilization procedure.

Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of APG1252 administration. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Pregnant women are excluded from this study because the agent used in this study has the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:

   • Postmenopausal (no menses in greater than or equal to 12 consecutive months).
   • History of hysterectomy or bilateral salpingo-oophorectomy.
   • Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
   • History of bilateral tubal ligation or another surgical sterilization procedure.
2. Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
3. Patient with documented hypersensitivity to any of the components of the therapy program.
4. Patients with known active, uncontrolled CNS leukemia will not be eligible.
5. Patients with prior treatment with a BCL-XL inhibitor will not be eligible.
6. Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.
7. Known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies) unless HIV RNA is undetectable by PCR.
8. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment or at risk for HBV reactivation. Hepatitis B virus DNA and HCV RNA must be undetectable upon testing. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive. Prior test results obtained as part of standard of care that confirm a subject is immune and not at risk for reactivation (ie, hepatitis B surface antigen negative, surface antibody positive) may be used for purposes of eligibility and tests do not need to be repeated. Subjects with prior positive serology results must have negative polymerase chain reaction results. Subjects whose immune status is unknown or uncertain must have results confirming immune status before enrollment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Part II Cohort A Treatment with Azacitidine (IV or SQ) + APG1252 (IV) Q4W R/R AML; Treatment will be administered on an inpatient or outpatient basis. All induction and consolidation intravenous infusions of APG-1252 will be administered at MD Anderson Cancer Center (MDACC).	Drug: Azacitidine; Given by IV; Other Names: Vidaza; Onureg; Drug: APG1252; Given by IV; Other Names: Pelcitoclax
Experimental: Cohort B: Part II Cohort B Treatment with Azacitidine (IV or SQ)+APG1252 (IV) Q4W untreated AML; Treatment will be administered on an inpatient or outpatient basis. All induction and consolidation intravenous infusions of APG-1252 will be administered at MD Anderson Cancer Center (MDACC).	Drug: Azacitidine; Given by IV; Other Names: Vidaza; Onureg; Drug: APG1252; Given by IV; Other Names: Pelcitoclax
Experimental: Lead-In: Part I Lead-In Treatment with Azacitidine (IV or SQ) + APG1252 (IV) Q4W R/R AML; Treatment will be administered on an inpatient or outpatient basis. All induction and consolidation intravenous infusions of APG-1252 will be administered at MD Anderson Cancer Center (MDACC).	Drug: Azacitidine; Given by IV; Other Names: Vidaza; Onureg; Drug: APG1252; Given by IV; Other Names: Pelcitoclax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Tapan Kadia, MD, UT MD Anderson

Publications and helpful links

Helpful Links

• UT MD Anderson Website

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2026
• Primary Completion (Estimated): December 12, 2029
• Study Completion (Estimated): December 12, 2031

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; pelcitoclax
• Other Study ID Numbers: 2025-1579; NCI-2026-02429 (Other Identifier: NCI-CTRP Clinical Trials Registray)

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