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

NCT04188405 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2019-0610NCI-2019-07594
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Myeloid Leukemia; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Acute Myeloid Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Acute Myeloid Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Defined as the proportion of patients achieving complete remission (CR) + CR with incomplete count recovery (CRi) occurring at the end of 2 cycles of treatment. Will be estimated along with the 95% credible interval. Patients who drop out of the study before completing 2 cycles and have been treated will be censored for the primary endpoint analysis.

  End of cycle 2 (each cycle is 28 days)

Secondary Outcomes (5)

• Rate of minimal residual disease negativity

  Up to 4.5 years

• Proportion of patients proceeding to allogeneic stem cell transplant

  Up to 4.5 years

• Relapse-free survival (RFS)

  From the date of treatment initiation to the date of documented treatment relapses from CR/CRi or death from any cause, whichever occurs first, assessed up to 4.5 years

• Overall survival (OS)

  From treatment start till death or last follow-up, assessed up to 4.5 years

• Incidence of adverse events

  Up to 4.5 years

Other Outcomes (1)

• Apoptotic protein expression and Bcl-2 dependency on response and resistance

  Up to 4.5 years

Study Arms (1)

Treatment (ponatinib, venetoclax, decitabine)

EXPERIMENTAL

See Detailed Description.

Drug: Decitabine; Drug: Ponatinib; Drug: Venetoclax

Interventions

Decitabine DRUG

Given IV

Also known as: 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (ponatinib, venetoclax, decitabine)

Ponatinib DRUG

Given PO

Also known as: AP-24534, AP24534

Treatment (ponatinib, venetoclax, decitabine)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (ponatinib, venetoclax, decitabine)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Short NJ, Nguyen D, Jabbour E, Senapati J, Zeng Z, Issa GC, Abbas H, Nasnas C, Qiao W, Huang X, Borthakur G, Chien K, Haddad FG, Pemmaraju N, Karrar OS, Nguyen D, Konopleva M, Kantarjian H, Ravandi F. Decitabine, venetoclax, and ponatinib for advanced phase chronic myeloid leukaemia and Philadelphia chromosome-positive acute myeloid leukaemia: a single-arm, single-centre phase 2 trial. Lancet Haematol. 2024 Nov;11(11):e839-e849. doi: 10.1016/S2352-3026(24)00250-3. Epub 2024 Sep 17.

  PMID: 39303729 DERIVED

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Acute; Blast Crisis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Decitabine; Injections; ponatinib; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes

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; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Nicholas Short

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2019
• First Posted: December 5, 2019
• Study Start: May 17, 2020
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: November 20, 2025

Record last verified: 2025-11

Locations

US (1)