Dasatinib in Treating Patients With Early Chronic Phase Chronic Myelogenous Leukemia

Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) With Dasatinib (BMS-354825)

The goal of this clinical research study is to learn if BMS-354825 (dasatinib) can help to control CML in chronic phase. The safety of this drug will also be studied.

Study Overview

• Status: Completed
• Conditions: Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia
• Intervention / Treatment: Drug: Dasatinib

Detailed Description

Dasatinib is an anticancer drug that is designed to block the function of BCR-ABL, which is the abnormal protein responsible for causing leukemia in certain cells.

Before you can start therapy on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in the study. You will have a complete medical history and physical exam. Blood (about 2 tablespoons) will be collected for routine tests. You will also have a bone marrow biopsy and aspiration. To collect a bone marrow biopsy and aspiration, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow and bone is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test. If you are found to be eligible to take part in this study and you agree, you will take dasatinib once every day while on study. Dasatinib should be taken by mouth with water.

Every 1-2 weeks during the first 4 weeks of the study, you will have around 2 tablespoons of blood drawn for routine blood tests. The blood tests will be repeated every 4-6 weeks until 1 year from when you started therapy and then every 3-4 months until 2 years, then as often as the doctor thinks it is needed. A bone marrow aspiration will also be taken to check the status of the disease every 3-4 months for the first year and then as often as the doctor thinks it is needed for as long as you are on the study.

You will be given a medication diary to monitor any missed doses. You will also be asked to visit the doctor for a physical exam and to have vital signs measured periodically. These visits will be scheduled at least every 3-4 months for the first year, then recommended every 6 to 12 months while you are on the study. The visits may be scheduled more often depending on the status of the disease.

Treatment may be continued for up to 8-10 years or as long as the doctor feels it is necessary to control the leukemia. If the disease gets worse or you experience any intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you. If you decide to stop participating in the study, you are encouraged to discuss your decision with your study doctor.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of Ph-positive or Bcr-Abl positive CML in early chronic phase CML (i.e., time from diagnosis </= 12 months). Except for hydroxyurea, patients must have received no or minimal prior therapy, defined as <1 month (30 days) of prior IFN-alpha (with or without ara-C) and/or an FDA approved TKI
• Continued from above #1: Clonal evolution defined as the presence of additional chromosomal abnormalities other than the Ph chromosome has been 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
• Age >/= 16 years (Age >18 years to participate in optional symptom burden assessment)
• ECOG performance of 0-2
• Adequate end organ function, defined as the following: total bilirubin <1.5 x ULN, SGPT <2.5x ULN, creatinine <1.5x 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.
• Reliable telephone access to receive calls from an interactive voice response system (IVR) (only applicable to patients who will participate in optional symptom burden assessment)

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 QTc interval on pre-entry electrocardiogram (> 450 msec) on both the Fridericia and Bazett's correction; Uncontrolled hypertension; History of significant bleeding disorder unrelated to cancer, including:
• Cont: Diagnosed congenital bleeding disorders (von Willebrand's disease) Diagnosed acquired bleeding disorder w/in 1 year (acquired anti-factor VIII antibodies);Pts currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including: quinidine, procainamide, disopyramide amiodarone, sotalol, ibutilide, dofetilide erythromycins, clarithromycin chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
• Patients with active, uncontrolled psychiatric disorders including: psychosis, major depression, and bipolar disorders
• Women of pregnancy potential must practice 2 effective methods 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.
• Continued: 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 investigational product and must not be enrolled in the study.
• Patients in late chronic phase (i.e., time from diagnosis to treatment >12 months), accelerated or blast phase are excluded.
• The definitions of CML phases are as follows: a) Early chronic phase: time from diagnosis to therapy </= 12 months; Late chronic phase: time from diagnosis to therapy > 12 months, b) Blastic phase: presence of 30% blasts or more in the peripheral blood or bone marrow, c) 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)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dasatinib; Patients receive dasatinib PO QD for up to 15-18 years.	Drug: Dasatinib; Given PO; Other Names: BMS-354825; Dasatinib Hydrate; Dasatinib Monohydrate; Sprycel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Major Molecular Response at 12 Months	Major Molecular Response (MMR) is BCR-ABL/ABL ratio </= 0.05	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time from date of treatment start until date of death due to any cause or last Follow-up.	Up to 19 years, 4 months and 6 days
Participants With Complete Cytogenic Response (CCR)	Complete Cytogenic Response (CCR) is Ph positive 0%	Up to 19 years, 4 months and 6 days
Participants Who Developed the ABL Mutations	ABL mutations will be assesses during treatment through Quanitiative PCR (qPCR) (RT-qPCR) or ABM mutational analysis using Sanger Sequencing or next-Generation Sequencing (NGS).	Up to 19 years, 4 months and 6 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom burden during dasatinib therapy (optional)	Frequency tables will be used to summarize M. D. Anderson Symptom Inventory (MDASI)-CML and single-item quality of life (QOL) variables. Logistic regression will be used to assess the impact of patient characteristics on symptom severity, interference, and QOL.	Up to 12 months after last dose of study treatment
Symptom severity during dasatinib therapy	Logistic regression will be used to assess the impact of patient characteristics on symptom severity, interference, and QOL.	Up to 12 months after last dose of study treatment
Therapy adherence during dasatinib therapy	Logistic regression will be used to assess the impact of patient characteristics on symptom severity, interference, and QOL.	Up to 12 months after last dose of study treatment
Quality of life during dasatinib therapy	Logistic regression will be used to assess the impact of patient characteristics on symptom severity, interference, and QOL (quality of life).	Up to 12 months after last dose of study treatment

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Lucia Masarova, MD, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• Jain P, Kantarjian H, Boddu PC, Nogueras-Gonzalez GM, Verstovsek S, Garcia-Manero G, Borthakur G, Sasaki K, Kadia TM, Sam P, Ahaneku H, O'Brien S, Estrov Z, Ravandi F, Jabbour E, Cortes JE. Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs. Blood Adv. 2019 Mar 26;3(6):851-861. doi: 10.1182/bloodadvances.2018025874.
• Issa GC, Kantarjian HM, Gonzalez GN, Borthakur G, Tang G, Wierda W, Sasaki K, Short NJ, Ravandi F, Kadia T, Patel K, Luthra R, Ferrajoli A, Garcia-Manero G, Rios MB, Dellasala S, Jabbour E, Cortes JE. Clonal chromosomal abnormalities appearing in Philadelphia chromosome-negative metaphases during CML treatment. Blood. 2017 Nov 9;130(19):2084-2091. doi: 10.1182/blood-2017-07-792143. Epub 2017 Aug 23.
• Jain P, Kantarjian H, Nazha A, O'Brien S, Jabbour E, Romo CG, Pierce S, Cardenas-Turanzas M, Verstovsek S, Borthakur G, Ravandi F, Quintas-Cardama A, Cortes J. Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia: results with four tyrosine kinase inhibitor modalities. Blood. 2013 Jun 13;121(24):4867-74. doi: 10.1182/blood-2013-03-490128. Epub 2013 Apr 25.

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2005
• Primary Completion (Actual): March 14, 2025
• Study Completion (Actual): March 14, 2025

Study Registration Dates

• First Submitted: November 14, 2005
• First Submitted That Met QC Criteria: November 14, 2005
• First Posted (Estimated): November 16, 2005

Study Record Updates

• Last Update Posted (Estimated): January 15, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia; Myeloproliferative Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Pyrimidines; Dasatinib
• Other Study ID Numbers: 2005-0422 (Other Identifier: M D Anderson Cancer Center); NCI-2012-01317 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); NCI-2010-00440

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No