- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05007873
ASTX727 and Dasatinib for the Treatment of Newly Diagnosed Philadelphia Chromosome or BCR-ABL Positive Chronic Myeloid Leukemia in Chronic Phase
Phase II Study Assessing Safety and Clinical Activity of the Combination of ASTX727 With Dasatinib in Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVE:
I. To estimate the proportion of patients with previously-untreated chronic phase chronic myeloid leukemia (CML) who achieve molecular response 4 (MR4) after 6-months of the combination of decitabine and cedazuridine (ASTX727) and dasatinib 50 mg daily.
SECONDARY OBJECTIVES:
I. To estimate the proportion of patients with previously-untreated chronic phase CML who achieve MR4 after both the 3-months of the combination of ASTX727 and dasatinib 50 mg daily.
II. To estimate cumulative overall rate of molecular response 4.5 (MR4.5). III. To estimate the 12-months major molecular response (MMR) rate. IV. To estimate the proportion of patients with MR4.5 at 6-, 12-, 18-, 24-, and 36-months of therapy.
V. To estimate the proportion of patients with sustained MR4.5 of 3 years and more.
VI. To estimate the treatment-free remission rate (TFR), time to progression, and overall survival.
VII. To assess the safety of this combination.
OUTLINE:
Patients receive dasatinib orally (PO) once daily (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.
After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- M D Anderson Cancer Center
-
Contact:
- Elias Jabbour
- Phone Number: 713-792-4764
- Email: ejabbour@mdanderson.org
-
Principal Investigator:
- Elias Jabbour
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
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 and no other criteria for accelerated phase will be eligible for this study
- Eastern Cooperative Oncology Group (ECOG) performance of 0-2
- Total bilirubin < 1.5 x upper limit of normal (ULN) (unless secondary to Gilbert's disease, in which case should be < 2.5 x ULN)
- Serum glutamic pyruvic transaminase (SGPT) < 3 x ULN
- Creatinine < 1.5 x ULN
- 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
Exclusion Criteria:
- 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:
- 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. Pregnant or breast-feeding women are excluded. All WOCBP must have a negative pregnancy test prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive study drug and must not be enrolled in the study
Patients in late chronic phase (i.e., time from diagnosis to treatment > 12 months), accelerated (except as noted in inclusion criteria) or blast phase are excluded. The definitions of CML phases are as follows:
- Early chronic phase: time from diagnosis to therapy =< 12 months
- Late chronic phase: time from diagnosis to therapy > 12 months
- Blastic phase: presence of 30% blasts or more in the peripheral blood or bone marrow
Accelerated phase CML: presence of any of the following features:
- Peripheral or marrow blasts 15% or more
- Peripheral or marrow basophils 20% or more
- Thrombocytopenia < 100 x 10^9/L unrelated to therapy
- Documented extramedullary blastic disease outside liver or spleen
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (dasatinib, decitabine and cedazuridine)
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. |
Given PO
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of molecular response 4 (MR4)
Time Frame: At 6 months
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of MR4.5
Time Frame: At 12 months
|
Will be presented with 95% confidence 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 12 months
|
Major molecular response rate
Time Frame: At 12 months
|
Will be presented with 95% confidence 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 12 months
|
Treatment-free remission rate
Time Frame: Up to 15 years
|
Will be presented with 95% confidence intervals.
The association between molecular responses and demographic/ clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test.
|
Up to 15 years
|
Time to progression
Time Frame: Up to 15 years
|
Survival time will be estimated using the Kaplan-Meier method.
Patients who drop out of the study will be included in the time to event data as "censored data".
The two-sided log-rank test will be used to assess the differences of time to events between groups.
|
Up to 15 years
|
Overall survival
Time Frame: Up to 15 years
|
Survival time will be estimated using the Kaplan-Meier method.
Patients who drop out of the study will be included in the time to event data as "censored data".
The two-sided log-rank test will be used to assess the differences of time to events between groups.
|
Up to 15 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Elias Jabbour, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease Attributes
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Chromosome Aberrations
- Translocation, Genetic
- Chronic Disease
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Leukemia, Myeloid, Chronic-Phase
- Philadelphia Chromosome
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Decitabine
- Dasatinib
- Decitabine and cedazuridine drug combination
Other Study ID Numbers
- 2021-0271 (Other Identifier: M D Anderson Cancer Center)
- NCI-2021-08486 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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