ASTX727 and Dasatinib for the Treatment of Newly Diagnosed Philadelphia Chromosome or BCR-ABL Positive Chronic Myeloid Leukemia in Chronic Phase

NCT05007873 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-0271NCI-2021-08486
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the effect of ASTX727 and dasatinib in treating patients with newly diagnosed Philadelphia chromosome or BCR-ABL positive chronic myeloid leukemia in chronic phase. Philadelphia chromosome positive and BCR-ABL positive are types of genetic mutations (changes). Chemotherapy drugs, such as ASTX727, 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. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. ASTX727 and dasatinib may help to control Philadelphia chromosome-positive chronic myeloid leukemia or BCR-ABL positive chronic myeloid leukemia in chronic phase.

Conditions

Chronic Phase Chronic Myelogenous Leukemia; BCR-ABL1 Positive; Philadelphia Chromosome Positive; BCR-ABL1 Positive Chronic Myelogenous Leukemia

Outcome Measures

Primary Outcomes (1)

• Rate of molecular response 4 (MR4)

  Will be estimated with 95% credible intervals. The association between molecular responses and demographic/ clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test.

  At 6 months

Secondary Outcomes (5)

• Rate of MR4.5

  At 12 months

• Major molecular response rate

  At 12 months

• Treatment-free remission rate

  Up to 15 years

• Time to progression

  Up to 15 years

• Overall survival

  Up to 15 years

Study Arms (1)

Treatment (dasatinib, decitabine and cedazuridine)

EXPERIMENTAL

Patients receive dasatinib PO QD on days 1-28. Beginning cycle 4, patients also receive decitabine and cedazuridine PO QD on days 1-3. Cycles repeat every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive dasatinib PO QD on days 1-28. Cycles repeat every 28 days for up to 12 years in the absence of disease progression or unacceptable toxicity.

Drug: Dasatinib; Drug: Decitabine and Cedazuridine

Interventions

Dasatinib DRUG

Given PO

Also known as: BMS-354825, Dasatinib Hydrate, Dasatinib Monohydrate, Sprycel

Treatment (dasatinib, decitabine and cedazuridine)

Decitabine and Cedazuridine DRUG

Given PO

Also known as: ASTX727, C-DEC, CDA Inhibitor E7727/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Tablet, DEC-C, Inqovi

Treatment (dasatinib, decitabine and cedazuridine)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Philadelphia chromosome (Ph)-positive or BCR-ABL positive CML in early chronic phase CML (i.e., time from diagnosis ≤12 months). Except for hydroxyurea and/or 1 to 2 doses of cytarabine patients must have received no or minimal prior therapy, defined as \< 1 month (30 days) of prior Food and Drug Administration (FDA) approved tyrosine kinase inhibitor (TKI)
• Clonal evolution defined as the presence of additional chromosomal abnormalities other than the Ph chromosome has historically been included as a criterion for accelerated phase. However, patients with clonal evolution as the only criterion of accelerated phase have a significantly better prognosis, and when present at diagnosis may not impact the prognosis at all. Thus, patients with clonal evolution at diagnosis (early disease) and no other criteria for accelerated phase will be eligible for this study.
• Eastern Cooperative Oncology Group (ECOG) performance of 0-2
• Adequate end organ function, defined as the following: total bilirubin \<1.5x ULN (unless secondary to Gilbert's disease, in which case should be \< 2.5x ULN), SGPT \<3x ULN, creatinine clearance ≥ 30mL/min calculated using modified Crokcroft-Gault.
• Patients must sign an informed consent indicating they are aware of the investigational nature of this study, in keeping with the policies of the hospital.
• Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment.

You may not qualify if:

• New York Heart Association (NYHA) cardiac class 3-4 heart disease
• Cardiac Symptoms: Patients meeting the following criteria are not eligible unless cleared by Cardiology:
• Uncontrolled angina within 3 months
• Diagnosed or suspected congenital long QT syndrome
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
• Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (\> 460 msec)
• History of significant bleeding disorder unrelated to cancer, including unless cleared by hematologist or hemato-oncologist
• Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
• Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
• Patients with active, uncontrolled psychiatric disorders include: psychosis, major depression, and bipolar disorders
• Subject is known to be positive for human immunodeficiency virus (HIV) (HIV testing is not required)
• Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
• Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
• Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface \[HBs\] antigen negative-, anti-HBs antibody positive and anti-hepatitis B core \[HBc\] antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate
• Women of pregnancy potential must practice an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Women must continue birth control for the duration of the trial and at least 3 months after the last dose of study drug.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Astex Pharmaceuticals, Inc.: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase

Interventions

Dasatinib; decitabine and cedazuridine drug combination

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; 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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Elias Jabbour

  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: August 9, 2021
• First Posted: August 17, 2021
• Study Start: October 21, 2021
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): October 30, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Locations

US (1)