A Phase I Study of Decitabine, Lisaftoclax, and Olverembatinib in Patients With Advanced Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Myeloid Leukemia

NCT06401603 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2024-0032NCI-2024-03867
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To find the recommended doses of lisaftoclax and olverembatinib that can be given in combination with decitabine to participants with advanced CML and Ph+ AML.

Conditions

Philadelphia Chromosome-Positive Acute Myeloid Leukemia; Advanced Chronic Myeloid Leukemia

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)

Phase 1

EXPERIMENTAL

Participants enrolled in Phase I, the dose of lisaftoclax you receive will depend on when a participants join this study. Up to 2 dose levels of lisaftoclax will be tested. Between 3-12 participants will be enrolled at each dose level.

Drug: Decitabine; Drug: Listaftoclax; Drug: Olverembatinib

Phase 2

EXPERIMENTAL

Participants enrolled in Phase II, participants will receive lisaftoclax at the recommended dose that was found in Phase I

Drug: Decitabine; Drug: Listaftoclax; Drug: Olverembatinib

Interventions

Decitabine DRUG

Given by IV

Also known as: Dacogen

Phase 1; Phase 2

Listaftoclax DRUG

Given by PO

Phase 1; Phase 2

Olverembatinib DRUG

Given by PO

Phase 1; Phase 2

Eligibility Criteria

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

You may qualify if:

• a) Diagnosis: Age ≥18 years with CML-AP, CML-MBP, or Ph+ AML by WHO 2016 criteria.
• Participants must have been intolerant or resistant to at least one prior BCR::ABL1 TKI
• \. Performance status ≤3 (ECOG Scale).
• \. Adequate liver, cardiac, renal and pancreatic function as defined by the following criteria:
• Total serum bilirubin \< 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the PI
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 3 x ULN, unless due to the underlying leukemia approved by the PI
• Creatinine clearance ≥30 mL/min
• Serum amylase or lipase \< 1.5 x ULN
• \. Ability to understand and the willingness to sign a written informed consent document
• \. Willingness to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months after completion of study participation. For women of child-bearing potential, adequate methods of contraception include: complete abstinence,, 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.

You may not qualify if:

• Participants who have previously received lisaftoclax or olverembatinib
• History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
• Active grade III-V cardiac failure as defined by the New York Heart Association Criteria
• Clinically significant and uncontrolled cardiovascular disease, including but not restricted to:
• i. Myocardial infarction (MI), stroke, revascularization, unstable angina, or transient ischemic attack within 6 months.
• ii. Left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards prior to enrollment.
• iii. Diagnosed or suspected congenital long QT syndrome. iv. Clinically significant atrial or ventricular arrhythmias (such as uncontrolled, clinically significant atrial fibrillation, ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) as determined by the treating physician.
• v. Prolonged QTc interval on pre-entry electrocardiogram (\> 480 msec) unless corrected after electrolyte replacement.
• vi. History of venous thromboembolism including deep venous thrombosis or pulmonary embolism within the past 3 months, excluding line associated DVT of the upper extremity vii. Uncontrolled hypertension (diastolic blood pressure \>100mmHg; and systolic \>150mmHg).
• Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment).
• Active central nervous system leukemia
• Known human immunodeficiency virus (HIV) seropositive, unless well-controlled on stable doses of anti-retroviral therapy.
• Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection Note: Participants who have isolated positive hepatitis B core antibody (ie, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Participants who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load.
• Participants with a prior or concurrent malignancy whose natural history or treatment is not anticipated to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the PI
• Consumed strong inducer of CYP3A or p-glycoprotein within 14 days of study enrollment, or 5 half-lives, whichever is longer. Agents include but are not limited to: carbamazepine, phenytoin, rifampin, and St. John's wart

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Ascentage Pharma Group Inc.: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

Decitabine; olverembatinib

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Nicholas Short, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicholas Short, MD

CONTACT

(713) 563-4485; nshort@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: May 2, 2024
• First Posted: May 6, 2024
• Study Start: August 6, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (1)