A Phase 3 interventional study of Dasatinib and Imatinib in Myeloid Leukemia, Chronic, sponsored by Bristol-Myers Squibb. Completed at 109 sites in 27 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-02-15.
Sponsored by Bristol-Myers Squibb · Phase 3, Interventional, and Treatment
The purpose of this clinical research study is to compare the confirmed complete cytogenetic response of dasatinib with that of imatinib within 12 months after randomization in patients with newly diagnosed chronic-phase Philadelphia positive chronic myeloid leukemia. The safety of this treatment will also be studied.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 547 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.
Browse Leukemia studies →Bristol-Myers Squibb is the lead sponsor of 1,538 studies on the registry; 116 are open to participants now.
Of its 429 completed or terminated interventional studies of FDA-regulated products, 223 (52%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
Drug: Dasatinib
Drug: Imatinib
Tablets, oral, dasatinib 50-140 mg once daily (QD)
Also known as: Sprycel®, BMS-354825
Tablets, oral, imatinib 200-800 mg, QD
Number of Participants With Best Confirmed Complete Cytogenetic Response (cCCyR) Within 12 Months
Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from bone marrow (BM) sample. (Ideally, 25 metaphases but at least 20 metaphases from a BM sample were evaluated). Complete Cytogenetic Response (CCyR)=0% Ph+ cells in metaphase in BM. A cCCyR=those in which all measurements up to at least 28 days after the initial response show an equivalent or better CCyR.
Time frame: Pretreatment, every 3 months up to 12 months
Percentage of Participants Remaining in Confirmed Complete Cytogenetic Response (cCCyR)
Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from bone marrow (BM) sample. (Ideally, 25 metaphases but at least 20 metaphases from a BM sample were evaluated). Complete Cytogenetic Response (CCyR)=0% Ph+ cells in metaphase in BM. A cCCyR=those in which all measurements up to at least 28 days after the initial response show an equivalent or better CCyR. Percentage of participants in cCCyR at years 2, 3, 4 and 5 was computed for all randomized participants who achieved cCCyR as measured from the time of first confirmation until the date of progression or death. Participants with cCCyR who neither progress nor die are censored on the date of their last cytogenetic assessment. Participants without cCCyR are considered to have progressed on Day 1.
Time frame: Years 2, 3, 4 and 5
Percentage of Participants With Major Molecular Response (MMR) at Any Time
Molecular response was assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).
Time frame: Planned total follow-up duration of 5 years
Time to Confirmed Complete Cytogenic Response (cCCyR) Overall
The time to cCCyR for all randomized participants is defined as the time from the randomization date until criteria are first met for complete cytogenic response (provided it is confirmed later). The time to cCCyR analysis censors nonresponders who do not progress at their last cytogenetic assessments and nonresponders who progress at the maximum time of all randomized participants. .
Time frame: Day 1 to 5 years
Time to Major Molecular Response (MMR) Overall
The time to MMR for all randomized participants is defined as the time from randomization date until measurement criteria are first met for MMR. The time to MMR analysis censors nonresponders who do not progress at their last molecular assessments and nonresponders who progress at the maximum time of all randomized participants.
Time frame: Day 1 to 5 years
Percentage of Participants With Progression-free Survival (PFS)
PFS was defined as the time from randomization until progression (any progression/death within 30 days of last dosing date, or between 30-60 days of last dosing prior to start of secondary therapy). Those who did not progress/die or who progressed/died after 60 days of last dose were censored at last on-study hematologic/cytogenetic assessment; those with progression/death 30-60 days of last dosing date and after start date of secondary therapy censored at last on-study hematologic/cytogenetic assessment prior to start of secondary therapy; those who had not received study treatment censored on date randomized.
Time frame: Participants were followed-up for at least 5 years
Percentage of Participants With Overall Survival (OS)
OS was defined as the time from randomization to the date of death. If the participant had not died, survival was censored on last date the participant was known to be alive.
Time frame: Participants were followed-up for at least 5 years
Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Serious Adverse Events (SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Time frame: From date of last person, first visit to date of last person, last visit (approximately 8 years)
Number of Participants With Grade 3/4 Abnormalities in On-study Laboratory Test Results
ULN=upper limit of normal. Grade 3=Severe AE; Grade 4=Life-threatening or disabling AE. Absolute neutrophil count: Grade 3 \<1000-500/mm\^3; Grade 4 \<500/mm\^3. Hemoglobin: Grade 3 \<8.0-6.5 g/dL; Grade 4 \<6.5 g/dL. Platelets: Grade 3 \<50,000-25,000/mm\^3; Grade 4 \<25,000/mm\^3. ALT/AST: Grade 3 \>5.0-20\*ULN; Grade 4 \>20\*ULN. Total bilirubin: Grade 3 \>3-10\*ULN; Grade 4 \>10\*ULN. Sample normal ranges (may vary by institution): ALT, Female: 7-30 U/L, Male: 10-55 U/L; AST, Female: 9-25 U/L, Male10-40 U/L; Total bilirubin: 0.0-1.0 mg/dL. Creatinine: Grade 3 \>3.0-6.0\*ULN; Grade 4 \>6.0\*ULN. Phosphate: Grade 3 \<2.0-1.0 mg/dL; Grade 4 \<1.0 mg/dL. Calcium: Grade 3 \<7.0-6.0 mg/dL; Grade 4 \<6.0 mg/dL. Potassium: Grade 3 \<3.0-2.5 mmol/L; Grade 4 \<2.5 mmol/L.
Time frame: From date of last person, first visit to date of last person, last visit (approximately 8 years)
| Milestone | Dasatinib | Imatinib |
|---|---|---|
| Started | 259 | 260 |
| Received treatment | 258 | 258 |
| Completed | 0 | 0 |
| Not completed | 259 | 260 |
| Withdrew: Death | 0 | 1 |
| Withdrew: Disease progression | 18 | 22 |
| Withdrew: Intolerance | 42 | 17 |
| Withdrew: Treatment failure | 10 | 14 |
| Withdrew: Ae unrelated to study drug | 13 | 4 |
| Withdrew: Withdrawal by subject | 8 | 13 |
| Withdrew: Pregnancy | 2 | 1 |
| Withdrew: Lost to follow-up | 1 | 2 |
| Withdrew: Poor compliance/noncompliance | 1 | 7 |
| Withdrew: Administrative reason by sponsor | 157 | 162 |
| Withdrew: Varied | 6 | 15 |
| Withdrew: Did not receive treatment | 1 | 2 |
Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from bone marrow (BM) sample. (Ideally, 25 metaphases but at least 20 metaphases from a BM sample were evaluated). Complete Cytogenetic Response (CCyR)=0% Ph+ cells in metaphase in BM. A cCCyR=those in which all measurements up to at least 28 days after the initial response show an equivalent or better CCyR.
| Participants | Dasatinib | Imatinib |
|---|---|---|
| Number of Participants With Best Confirmed Complete Cytogenetic Response (cCCyR) Within 12 Months | 204 | 177 |
Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from bone marrow (BM) sample. (Ideally, 25 metaphases but at least 20 metaphases from a BM sample were evaluated). Complete Cytogenetic Response (CCyR)=0% Ph+ cells in metaphase in BM. A cCCyR=those in which all measurements up to at least 28 days after the initial response show an equivalent or better CCyR. Percentage of participants in cCCyR at years 2, 3, 4 and 5 was computed for all randomized participants who achieved cCCyR as measured from the time of first confirmation until the date of progression or death. Participants with cCCyR who neither progress nor die are censored on the date of their last cytogenetic assessment. Participants without cCCyR are considered to have progressed on Day 1.
| percentage of participants | Dasatinib | Imatinib |
|---|---|---|
| At Year 2 | 98.0 (94.7 to 99.2) | 96.9 (93.2 to 98.6) |
| At Year 3 | 96.9 (93.3 to 98.6) | 95.7 (91.6 to 97.8) |
| At Year 4 | 95.6 (91.4 to 97.8) | 95.7 (91.6 to 97.8) |
| At Year 5 | 93.1 (86.5 to 96.5) | 91.0 (83.6 to 95.2) |
Molecular response was assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).
| Percentage of participants | Dasatinib | Imatinib |
|---|---|---|
| Percentage of Participants With Major Molecular Response (MMR) at Any Time | 76.4 | 64.2 |
The time to cCCyR for all randomized participants is defined as the time from the randomization date until criteria are first met for complete cytogenic response (provided it is confirmed later). The time to cCCyR analysis censors nonresponders who do not progress at their last cytogenetic assessments and nonresponders who progress at the maximum time of all randomized participants. .
| Months | Dasatinib | Imatinib |
|---|---|---|
| Time to Confirmed Complete Cytogenic Response (cCCyR) Overall | 3.1 (3.0 to 3.1) | 5.8 (5.6 to 6.0) |
The time to MMR for all randomized participants is defined as the time from randomization date until measurement criteria are first met for MMR. The time to MMR analysis censors nonresponders who do not progress at their last molecular assessments and nonresponders who progress at the maximum time of all randomized participants.
| Months | Dasatinib | Imatinib |
|---|---|---|
| Time to Major Molecular Response (MMR) Overall | 9.3 (8.8 to 11.8) | 15.0 (12.2 to 18.2) |
PFS was defined as the time from randomization until progression (any progression/death within 30 days of last dosing date, or between 30-60 days of last dosing prior to start of secondary therapy). Those who did not progress/die or who progressed/died after 60 days of last dose were censored at last on-study hematologic/cytogenetic assessment; those with progression/death 30-60 days of last dosing date and after start date of secondary therapy censored at last on-study hematologic/cytogenetic assessment prior to start of secondary therapy; those who had not received study treatment censored on date randomized.
| Percentage of participants | Dasatinib | Imatinib |
|---|---|---|
| Percentage of Participants With Progression-free Survival (PFS) | 88.9 | 89.2 |
OS was defined as the time from randomization to the date of death. If the participant had not died, survival was censored on last date the participant was known to be alive.
| Percentage of participants | Dasatinib | Imatinib |
|---|---|---|
| Percentage of Participants With Overall Survival (OS) | 90.9 | 89.6 |
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
| Participants | Dasatinib | Imatinib |
|---|---|---|
| All AEs | 251 | 251 |
| All Drug-related AEs | 224 | 231 |
| Diarrhea | 100 | 91 |
| Pleural effusion | 74 | 3 |
| Nausea | 40 | 74 |
| Cough | 68 | 28 |
| Muscle spasms | 14 | 63 |
| Thrombocytopenia | 61 | 50 |
| Neutropenia | 60 | 49 |
| Headache | 59 | 46 |
| Pyrexia | 58 | 51 |
| Vomiting | 43 | 54 |
| SAEs | 90 | 70 |
| Drug-related SAEs | 43 | 22 |
| AEs leading to discontinuation | 51 | 26 |
| All deaths | 26 | 26 |
ULN=upper limit of normal. Grade 3=Severe AE; Grade 4=Life-threatening or disabling AE. Absolute neutrophil count: Grade 3 \<1000-500/mm\^3; Grade 4 \<500/mm\^3. Hemoglobin: Grade 3 \<8.0-6.5 g/dL; Grade 4 \<6.5 g/dL. Platelets: Grade 3 \<50,000-25,000/mm\^3; Grade 4 \<25,000/mm\^3. ALT/AST: Grade 3 \>5.0-20\*ULN; Grade 4 \>20\*ULN. Total bilirubin: Grade 3 \>3-10\*ULN; Grade 4 \>10\*ULN. Sample normal ranges (may vary by institution): ALT, Female: 7-30 U/L, Male: 10-55 U/L; AST, Female: 9-25 U/L, Male10-40 U/L; Total bilirubin: 0.0-1.0 mg/dL. Creatinine: Grade 3 \>3.0-6.0\*ULN; Grade 4 \>6.0\*ULN. Phosphate: Grade 3 \<2.0-1.0 mg/dL; Grade 4 \<1.0 mg/dL. Calcium: Grade 3 \<7.0-6.0 mg/dL; Grade 4 \<6.0 mg/dL. Potassium: Grade 3 \<3.0-2.5 mmol/L; Grade 4 \<2.5 mmol/L.
| Participants | Dasatinib | Imatinib |
|---|---|---|
| Grade 3/4 Absolute neutrophil count | 74 | 61 |
| Grade 3/4 Hemoglobin | 35 | 23 |
| Grade 3/4 Platelets | 56 | 37 |
| Grade 3/4 Alanine aminotransferase (ALT) | 2 | 4 |
| Grade 3/4 Aspartate aminotransferase (AST) | 2 | 3 |
| Grade 3/4 Total bilirubin | 3 | 0 |
| Grade 3/4 Creatinine | 3 | 2 |
| Grade 3/4 Phosphate | 19 | 79 |
| Grade 3/4 Calcium | 9 | 7 |
| Grade 3/4 Potassium | 0 | 8 |
Collected over Randomization to end of study (December 2015). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dasatinib | — | 90/258 (34.9%) | 216/258 (83.7%) |
| Imatinib | — | 70/258 (27.1%) | 231/258 (89.5%) |
| Event | Dasatinib | Imatinib |
|---|---|---|
| PLEURAL EFFUSIONRespiratory, thoracic and mediastinal disorders | 13/258 | 1/258 |
| PULMONARY HYPERTENSIONRespiratory, thoracic and mediastinal disorders | 7/258 | 0/258 |
| ABDOMINAL PAINGastrointestinal disorders | 5/258 | 1/258 |
| DIARRHOEAGastrointestinal disorders | 5/258 | 3/258 |
| ANAEMIABlood and lymphatic system disorders | 4/258 | 1/258 |
| THROMBOCYTOPENIABlood and lymphatic system disorders | 4/258 | 4/258 |
| BLAST CELL IN MYELOGENOUS LEUKAEMIANeoplasms benign, malignant and unspecified (incl cysts and polyps) | 3/258 | 4/258 |
| FEBRILE NEUTROPENIABlood and lymphatic system disorders | 0/258 | 3/258 |
| ACUTE MYOCARDIAL INFARCTIONCardiac disorders | 3/258 | 1/258 |
| CARDIAC FAILURE CONGESTIVECardiac disorders | 3/258 | 0/258 |
| Event | Dasatinib | Imatinib |
|---|---|---|
| DIARRHOEAGastrointestinal disorders | 99/258 | 89/258 |
| NAUSEAGastrointestinal disorders | 40/258 | 74/258 |
| PLEURAL EFFUSIONRespiratory, thoracic and mediastinal disorders | 69/258 | 3/258 |
| COUGHRespiratory, thoracic and mediastinal disorders | 68/258 | 28/258 |
| MUSCLE SPASMSMusculoskeletal and connective tissue disorders | 14/258 | 63/258 |
| NEUTROPENIABlood and lymphatic system disorders | 60/258 | 49/258 |
| THROMBOCYTOPENIABlood and lymphatic system disorders | 59/258 | 48/258 |
| HEADACHENervous system disorders | 59/258 | 46/258 |
| PYREXIAGeneral disorders | 58/258 | 50/258 |
| VOMITINGGastrointestinal disorders | 41/258 | 52/258 |
| Age, Continuous(Years) | Dasatinib | Imatinib | Total |
|---|---|---|---|
| Mean | 46.4 ± 14.6 | 47.1 ± 13.9 | 46.7 ± 14.2 |
| Age, Customized(Participants) | Dasatinib | Imatinib | Total |
|---|---|---|---|
| <20 years | 5 | 9 | 14 |
| Between 21 and 45 years | 123 | 102 | 225 |
| Between 46 and 65 years | 111 | 125 | 236 |
| Between 66 and 75 years | 13 | 20 | 33 |
| >75 years | 7 | 4 | 11 |
| Gender(Participants) | Dasatinib | Imatinib | Total |
|---|---|---|---|
| Female | 115 | 97 | 212 |
| Male | 144 | 163 | 307 |
| Race/Ethnicity, Customized(Participants) | Dasatinib | Imatinib | Total |
|---|---|---|---|
| White | 132 | 143 | 275 |
| Black/African American | 2 | 1 | 3 |
| Asian | 108 | 95 | 203 |
| Other | 17 | 21 | 38 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status(Participants) | Dasatinib | Imatinib | Total |
|---|---|---|---|
| ECOG score=0 | 213 | 205 | 418 |
| ECOG score=1 | 46 | 53 | 99 |
| ECOG score=2 | 0 | 2 | 2 |
| Number of Patients With Liver Involvement(Participants) | Dasatinib | Imatinib | Total |
|---|---|---|---|
| Number | 37 | 18 | 55 |
| Number of Participants With Spleen Involvement(Participants) | Dasatinib | Imatinib | Total |
|---|---|---|---|
| Number | 83 | 71 | 154 |
Showing the first 100 of 109 sites across 27 countries.
This study is completed, as verified in Dec 2016. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Bristol-Myers Squibb