search
Back to results

Dasatinib in Treating Patients With Early Chronic Phase Chronic Myelogenous Leukemia

Primary Purpose

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

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dasatinib
Laboratory Biomarker Analysis
Pharmacological Study
Quality-of-Life Assessment
Questionnaire Administration
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 5) 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. 7) 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

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A (once daily dasatinib)

Arm B (twice daily dasatinib)

Arm Description

Patients receive dasatinib PO QD for up to 15-18 years.

Patients receive dasatinib PO BID for up to 15-18 years.

Outcomes

Primary Outcome Measures

Probability of major molecular response
Toxicity rate

Secondary Outcome Measures

Full Information

First Posted
November 14, 2005
Last Updated
June 1, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00254423
Brief Title
Dasatinib in Treating Patients With Early Chronic Phase Chronic Myelogenous Leukemia
Official Title
Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) With Dasatinib (BMS-354825)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 8, 2005 (Actual)
Primary Completion Date
November 30, 2024 (Anticipated)
Study Completion Date
November 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This randomized phase II trial studies how well dasatinib works in treating patients with early chronic phase chronic myelogenous leukemia. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVE: I. To estimate the proportion of patients with previously-untreated chronic phase chronic myelogenous leukemia (CML) attaining major molecular response by 12 months of treatment with dasatinib. SECONDARY OBJECTIVES: I. To estimate the proportion of patients with Philadelphia chromosome (Ph)-positive early chronic phase CML achieving a complete cytogenetic response after dasatinib therapy. II. To evaluate the durations of hematologic, cytogenetic and molecular response to dasatinib. III. To define the time to progression and overall survival for patients with CML in early chronic phase treated with dasatinib. IV. To evaluate the toxicity profile of dasatinib in patients with CML in early chronic phase. V. To evaluate the probability of developing c-abl oncogene 1, non-receptor tyrosine kinase (ABL) mutations for patients with CML in early chronic phase treated with dasatinib. VI. To analyze differences in response rates and in prognosis within different risk groups and patient characteristics. VII. To assess correlation between trough concentration and pleural effusion. VIII. To assess the inhibition of platelet function and assess correlation between drug concentration and degree of platelet inhibition. IX. To assess the effect of dasatinib therapy in bone metabolism as determined by changes in serum alkaline phosphatase (bone specific isoenzyme), and trabecular bone volume. X. To evaluate symptom burden in patients with CML receiving dasatinib. EXPLORATORY OBJECTIVE: I. To investigate the plasma/serum levels of specific micro ribonucleic acids (miRNAs) in CML patients receiving dasatinib as initial therapy for CML in chronic phase (CP). OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive dasatinib orally (PO) once daily (QD) for up to 15-18 years. ARM B: Patients receive dasatinib PO twice daily (BID) for up to 15-18 years. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
156 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A (once daily dasatinib)
Arm Type
Experimental
Arm Description
Patients receive dasatinib PO QD for up to 15-18 years.
Arm Title
Arm B (twice daily dasatinib)
Arm Type
Experimental
Arm Description
Patients receive dasatinib PO BID for up to 15-18 years.
Intervention Type
Drug
Intervention Name(s)
Dasatinib
Other Intervention Name(s)
BMS-354825, Dasatinib Hydrate, Dasatinib Monohydrate, Sprycel
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Pharmacological Study
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Probability of major molecular response
Time Frame
12 months
Title
Toxicity rate
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
Symptom burden during dasatinib therapy (optional)
Description
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.
Time Frame
Up to 12 months after last dose of study treatment
Title
Symptom severity during dasatinib therapy
Description
Logistic regression will be used to assess the impact of patient characteristics on symptom severity, interference, and QOL.
Time Frame
Up to 12 months after last dose of study treatment
Title
Therapy adherence during dasatinib therapy
Description
Logistic regression will be used to assess the impact of patient characteristics on symptom severity, interference, and QOL.
Time Frame
Up to 12 months after last dose of study treatment
Title
Quality of life during dasatinib therapy
Description
Logistic regression will be used to assess the impact of patient characteristics on symptom severity, interference, and QOL (quality of life).
Time Frame
Up to 12 months after last dose of study treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 5) 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. 7) 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lucia Masarova, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30885996
Citation
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.
Results Reference
derived
PubMed Identifier
28835440
Citation
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.
Results Reference
derived
PubMed Identifier
23620574
Citation
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.
Results Reference
derived
Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center

Learn more about this trial

Dasatinib in Treating Patients With Early Chronic Phase Chronic Myelogenous Leukemia

We'll reach out to this number within 24 hrs