Overview

Decitabine, Venetoclax, and Ponatinib for the Treatment of Philadelphia Chromosome-Positive Acute Myeloid Leukemia or Myeloid Blast Phase or Accelerated Phase Chronic Myelogenous Leukemia

Status:
Recruiting
Trial end date:
2024-09-01
Target enrollment:
0
Participant gender:
All
Summary
This phase II trial studies how well the combination of decitabine, venetoclax, and ponatinib work for the treatment of Philadelphia chromosome-positive acute myeloid leukemia or myeloid blast phase or accelerated phase chronic myelogenous leukemia. Drugs used in chemotherapy such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving decitabine, venetoclax, and ponatinib may help to control Philadelphia chromosome-positive acute myeloid leukemia or myeloid blast phase or accelerated phase chronic myelogenous leukemia.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
M.D. Anderson Cancer Center
Collaborator:
National Cancer Institute (NCI)
Treatments:
Decitabine
Ponatinib
Venetoclax
Criteria
Inclusion Criteria:

- Patients with Philadelphia (Ph)+ acute myeloid leukemia (AML) or myeloid accelerated
phase (AP)-chronic myelogenous leukemia (CML) or blast phase (BP)-CML (either t[9;22]
and/or BCR-ABL1 positive by fluorescent in situ hybridization or polymerase chain
reaction). Both untreated and relapsed/refractory patients are eligible

- Performance status =< 3 (Eastern Cooperative Oncology Group [ECOG] scale)

- Total serum bilirubin =< 2 x upper limit of normal (ULN), unless due to Gilbert's
syndrome, hemolysis or the underlying leukemia approved by the principal investigator
(PI)

- Alanine aminotransferase (ALT) =< 1.5 x ULN, unless due to the underlying leukemia
approved by the PI

- Aspartate aminotransferase (AST) =< 1.5 x ULN unless due to the underlying leukemia
approved by the PI

- Creatinine clearance >= 30 mL/min

- Serum lipase =< 1.5 x ULN

- Amylase =< 1.5 x ULN

- Ability to swallow

- Signed informed consent

Exclusion Criteria:

- Active serious infection not controlled by oral or intravenous antibiotics (e.g.
persistent fever or lack of improvement despite antimicrobial treatment)

- History of acute pancreatitis within 6 months of study or history of chronic
pancreatitis

- Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)

- Active secondary malignancy that in the investigator's opinion will shorten survival
to less than 1 year

- Active grade III-V cardiac failure as defined by the New York Heart Association
criteria

- Clinically significant, uncontrolled, or active cardiovascular disease, specifically
including, but not restricted to:

- Myocardial infarction (MI), stroke, revascularization, unstable angina or
transient ischemic attack within 6 months

- Left ventricular ejection fraction (LVEF) less than lower limit of normal per
local institutional standards prior to enrollment

- Diagnosed or suspected congenital long QT syndrome

- 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

- Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 480 msec)
unless corrected after electrolyte replacement

- History of venous thromboembolism including deep venous thrombosis or pulmonary
embolism within the past 3 months, excluding line-associated deep venous
thrombosis (DVT) of the upper extremity

- Uncontrolled hypertension (diastolic blood pressure > 100 mmHg; systolic > 150
mmHg)

- Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days
prior to starting venetoclax

- 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, or a Food and
Drug Administration (FDA)-approved BCR-ABL tyrosine kinase inhibitor (TKI) is
permitted

- Pregnant and lactating women will not be eligible; women of childbearing potential
should have a negative pregnancy test prior to entering on the study and be willing to
practice methods of contraception throughout the study period. Women do not have
childbearing potential if they have had a hysterectomy or are postmenopausal without
menses for 12 months. In addition, men enrolled on this study should understand the
risks to any sexual partner of childbearing potential and should practice an effective
method of birth control