Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia
Conditions
Brief summary
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.
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aspiration, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow and bone is withdrawn through a large needle.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.
Interventions
DRUGDasatinib
Given PO
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Major Molecular Response at 12 Months | 12 months | Major Molecular Response (MMR) is BCR-ABL/ABL ratio \</= 0.05 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 19 years, 4 months and 6 days | Time from date of treatment start until date of death due to any cause or last Follow-up. |
| Participants With Complete Cytogenic Response (CCR) | Up to 19 years, 4 months and 6 days | Complete Cytogenic Response (CCR) is Ph positive 0% |
| Participants Who Developed the ABL Mutations | Up to 19 years, 4 months and 6 days | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dasatinib Patients receive dasatinib PO QD for up to 15-18 years.
Dasatinib: Given PO | 150 |
| Total | 150 |
Baseline characteristics
| Characteristic | Dasatinib |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 135 Participants |
| Age, Continuous | 48 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 139 Participants |
| Region of Enrollment United States | 150 participants |
| Sex: Female, Male Female | 61 Participants |
| Sex: Female, Male Male | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 150 |
| other Total, other adverse events | 144 / 150 |
| serious Total, serious adverse events | 34 / 150 |
Outcome results
Primary
Number of Participants With a Major Molecular Response at 12 Months
Major Molecular Response (MMR) is BCR-ABL/ABL ratio \</= 0.05
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dasatinib | Number of Participants With a Major Molecular Response at 12 Months | 103 Participants |
Secondary
Overall Survival
Time from date of treatment start until date of death due to any cause or last Follow-up.
Time frame: Up to 19 years, 4 months and 6 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dasatinib | Overall Survival | NA Months |
Secondary
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).
Time frame: Up to 19 years, 4 months and 6 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dasatinib | Participants Who Developed the ABL Mutations | 7 Participants |
Secondary
Participants With Complete Cytogenic Response (CCR)
Complete Cytogenic Response (CCR) is Ph positive 0%
Time frame: Up to 19 years, 4 months and 6 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dasatinib | Participants With Complete Cytogenic Response (CCR) | 140 Participants |