Combination therapy for advanced chronic myeloid leukemia and acute myeloid leukemia

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

This study is testing a new combination of three drugs to see if it can help people with advanced chronic myeloid leukemia and a specific type of acute myeloid leukemia feel better and live longer.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (other)
• Drugs / interventions: olverembatinib, chemotherapy
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06401603 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to determine the recommended doses of the drugs lisaftoclax and olverembatinib when combined with decitabine for patients with advanced chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML). The study will assess the safety and efficacy of this combination therapy, including the rate of conversion to chronic phase CML and overall survival outcomes. Participants will undergo treatment and be monitored for various efficacy endpoints and safety assessments over multiple cycles.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced CML or Ph+ AML who have shown resistance or intolerance to at least one prior BCR::ABL1 TKI.

Not a fit: Patients who have not been diagnosed with advanced CML or Ph+ AML, or those who have not previously been treated with a BCR::ABL1 TKI may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with advanced CML and Ph+ AML who have not responded to previous therapies.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in hematologic malignancies, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

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

  2\. Performance status ≤3 (ECOG Scale).

  3\. Adequate liver, cardiac, renal and pancreatic function as defined by the following criteria:
  1. 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
  2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 3 x ULN, unless due to the underlying leukemia approved by the PI
  3. Creatinine clearance ≥30 mL/min
  4. Serum amylase or lipase \< 1.5 x ULN

     4\. Ability to understand and the willingness to sign a written informed consent document

     5\. 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.

     Exclusion Criteria:
     1. Participants who have previously received lisaftoclax or olverembatinib
     2. History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
     3. Active grade III-V cardiac failure as defined by the New York Heart Association Criteria
     4. 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).
     5. Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment).
     6. Active central nervous system leukemia
     7. Known human immunodeficiency virus (HIV) seropositive, unless well-controlled on stable doses of anti-retroviral therapy.
     8. 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.
     9. 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
     10. 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
     11. Treatment with any investigational antileukemic agents or chemotherapy agents in the last 7 days before study entry, unless full recovery from side effects has occurred or patient has rapidly progressive disease judged to be life-threatening by the investigator. Prior recent treatment with corticosteroids, hydroxyurea, cytarabine (up to 2 g/m2 given for cytoreduction within the preceding 7 days) and/or an FDA-approved BCR::ABL1 TKI is permitted.
     12. Inability to swallow
     13. Pregnant or breastfeeding women will not be eligible
     14. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Decitabine, Lisaftoclax, and Olverembatinib or other agents used in study.
     15. Participants with psychiatric illness/social situations that would limit compliance with study requirements.

Where this trial is running

Houston, Texas

• MD Anderson Cancer Center — Houston, Texas, United States (RECRUITING)

Study contacts

• Principal investigator: Nicholas Short, MD — M.D. Anderson Cancer Center
• Study coordinator: Nicholas Short, MD

Conditions: Advanced Chronic Myeloid Leukemia, Philadelphia Chromosome-Positive Acute Myeloid Leukemia