Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Leukemia, Myeloid, Chronic-Phase

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Dasatinib

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Tablets, Oral, 70 mg BID (AD CML) or 100 mg QD (Chronic CML), once or twice daily dependent on disease stage, until subjects meet discontinuation (DC) criteria for study

Bristol-Myers Squibb

The primary objective of this study is to estimate the major cytogenetic response (MCyR) rate to Dasatinib in subjects with CP CML, complete and overall hematologic response (CHR and OHR) rate in subjects with AD CML or Ph+ ALL who have primary or acquired resistance to imatinib, or are intolerant of imatinib, when administered at 100 mg QD (Chronic CML) or 70mg BID (AP CML and Ph+ALL).

Dasatinib in Imatinib Resistant/Intolerant Chinese CML (Chronic and Advanced Phase) Subjects

A Phase II Study to Determine the Activity of Dasatinib Administered Orally (PO) at a Dose of 100 mg Once Daily (QD) in Chronic Phase Chronic Myelogenous Leukemia (CML), at a Dose of 70 mg Twice Daily (BID) in Advanced Phase Chronic Myelogenous Leukemia (CML) Chinese Subjects Who Are Resistant to or Intolerant of Imatinib Mesylate (Gleevec®)

Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR) or Partial Cytogenetic Response (PCyR).

CCyR: 0% Ph-chromosome-positive cells in metaphase in bone marrow \[BM\] PCyR: 1-35% Ph-chromosome-positive cells in metaphase in \[BM\].

Major hematologic response: (MaHR) = complete hematologic response (CHR) + no evidence of leukemia (NEL).

CHR=white blood cells (WBC) ≤upper limit of normal (ULN); absolute neutrophil count (ANC) ≥1,000/mm3; platelets ≥100,000/mm3; no blasts/promyelocytes, \<20% basophils \& \<5% myelocytes+metamyelocytes in peripheral blood (PB); BM blasts ≤5%; no extra-medullary involvement/hepatomegaly/splenomegaly.

NEL=CHR except platelets ≥20,000/mm3 \& \<100,000/mm3; ANC \>500/mm3 \& \<1,000/mm3.

Overall hematologic response (OHR)=CHR+NEL+ return to chronic phase (RTC=\<15% blasts in BM and PB; \<30% blasts+promyelocytes in BM \& PB; \<20% basophils in PB; no extra-medullar disease other than spleen \& liver)

Complete Hematologic Response (CHR) is obtained when all the following criteria are met: WBC ≤ institutional ULN; platelets ≤ 450,000/mm3; ≤20% basophils in peripheral blood; no blasts or promyelocytes in PB cells; \< 5% myelocytes plus metamyelocytes in PB cells; no extra-medullary involvement including no hepatomegaly or splenomegaly.

Time to MCyR is defined as the time from the first dosing date until day criteria were first met for CCyR or PCyR, whichever occurred first.

Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR: 0% Ph-chromosome-positive cells in metaphase in BM) or Partial Cytogenetic Response (PCyR: 1-35% Ph-chromosome-positive cells in metaphase in BM).

The duration of time from when the first day all criteria are met for CCyR or PCyR until the date of progression or death. Participants who neither progress nor die will be censored on the date of their last cytogenetic assessment. The duration of MCyR will be estimated via the Kaplan-Meier product-limit method.

Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR: 0% Ph-chromosome-positive cells in metaphase in BM) or Partial Cytogenetic Response (PCyR: 1-35% Ph-chromosome-positive cells in metaphase in BM).

Progression-free survival is defined as the time from first dosing date until the time progressive disease (PD) is first documented. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who do not progress nor die will be censored on the date of their last hematologic or cytogenetic assessment, whichever comes last. PFS will be analyzed via the Kaplan-Meier product-limit method.

Participants were considered as having PD if they: achieved a hematologic response but subsequently no longer meet the criteria consistently on all assessment over a consecutive 2-week period after starting maximum dose; had no decrease from their baseline percent blasts in PB or BM on all assessments over a 4-week period, or had an increase by at least 50% in PB blast count (absolute) over a 2-week period after starting their maximum (individually-tolerated) dose.

The time from first dose of Dasatinib until the first day CHR or MaHR criteria are met (for all confirmed responses). Time to CHR is computed only for participants whose best response is CHR. Major HR (MaHR) includes CHR or no evidence of leukemia (NEL).

Major hematologic response: (MaHR) = complete hematologic response (CHR) + no evidence of leukemia (NEL).

CHR=white blood cells (WBC) ≤upper limit of normal (ULN); absolute neutrophil count (ANC) ≥1,000/mm3; platelets ≥100,000/mm3; no blasts/promyelocytes, \<20% basophils \& \<5% myelocytes+metamyelocytes in peripheral blood (PB); BM blasts ≤5%; no extra-medullary involvement/hepatomegaly/splenomegaly.

NEL=CHR except platelets ≥20,000/mm3 \& \<100,000/mm3; ANC \>500/mm3 \& \<1,000/mm3.

Time from the first day all criteria are met for CHR until the date treatment is discontinued due to progressive disease (PD) or death. Participants who neither progress nor die will be censored on the date of their last assessment.

CHR=white blood cells (WBC) ≤ upper limit of normal (ULN); absolute neutrophil count (ANC) ≥1,000/mm3; platelets ≥100,000/mm3; no blasts/promyelocytes, \<20% basophils and \<5% myelocytes+metamyelocytes in peripheral blood (PB); BM blasts ≤5%; no extra-medullary involvement/hepatomegaly/splenomegaly.

PD = Hematologic response achieved but subsequently no longer meet the criteria consistently on all assessment over a 2-week period;, and no decrease from their baseline percent blasts in PB or BM on all assessments over a 4-week period or have an increase by at least 50% in PB blast count (absolute) over a 2-week period.

Time from the first day all criteria are met for CHR or NEL or MaHR until the date of progression or death. Participants who neither progress nor die will be censored on the date of their last assessment.

MAHR = CHR or no evidence of leukemia (NEL). CHR=white blood cells (WBC) ≤ upper limit of normal (ULN); absolute neutrophil count (ANC) ≥1,000/mm3; platelets ≥100,000/mm3; no blasts/promyelocytes, \<20% basophils and \<5% myelocytes+metamyelocytes in peripheral blood (PB); BM blasts ≤5%; no extra-medullary involvement/hepatomegaly/splenomegaly.

NEL=CHR except platelets ≥20,000/mm3 and \<100,000/mm3; ANC \>500/mm3 and \<1,000/mm3.

Progressive disease (PD) = Hematologic response achieved but subsequently no longer meet the criteria consistently on all assessment over a 2-week period;, and no decrease from their baseline percent blasts in PB or BM on all assessments over a 4-week period or have an increase by at least 50% in PB blast count (absolute) over a 2-week period.

Progression-free survival is defined as the time from first dosing date until the time progressive disease (PD) is first documented. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who do not progress nor die will be censored on the date of their last hematologic or cytogenetic assessment whichever comes last. PFS will be analyzed via the Kaplan-Meier product-limit method.

Progressive disease (PD) = Hematologic response achieved but subsequently no longer meet the criteria consistently on all assessment over a 2-week period;, and no decrease from their baseline percent blasts in PB or BM on all assessments over a 4-week period or have an increase by at least 50% in PB blast count (absolute) over a 2-week period.

AEs and SAEs considered possibly, probably, or certainly related to study treatment, graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death).SAE= any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization/prolongation of existing hospitalization, results in persistent/significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

Mean dasatinib plasma concentrations following 70 mg BID dose in AD CML or Ph+ ALL participants and following 100 mg QD dose in CP CML participants

Cmax=maximum observed plasma concentration of dasatinib

Tmax=time of maximum observed plasma concentration. T-Half=plasma half-life.

Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration AUC(0-T)for dasatinib. AUC(INF)=area under the plasma concentration-time curve from time zero extrapolated to infinite time. AUC(TAU)=area under the plasma concentration-time curve for a dosing interval

Participants with AP advanced disease CML who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.

Advanced Disease CML - Accelerated Phase (AP)

Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.

Advanced Disease CML - Blast Phase/PH+ ALL

Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.

Chronic Phase (CP) CML

Total

Age, Continuous

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

China

Region of Enrollment

ECOG PS = 0

ECOG PS = 1

ECOG PS = 2

Not Reported

ECOG PS, a 6-item scale to assess disease progression, daily functioning, and appropriate treatment and prognosis. Scale: 0-5, with 0=Fully active, able to carry on all pre-disease performance without restriction and 5=Death. The inclusion criteria allowed only for scores of 0 to 2.

Eastern co-operative Oncology Group Performance Status (ECOG PS)

BMS Study Director

All treated participants with Chronic Phase Chronic Myeloid Leukemia (CP - CML). Data pre-specified to be collected in the Chronic Phase (CP) CML arm only.

Percentage of Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants With Major Cytogenetic Response (MCyR)

MaHR

All treated participants with Advanced Disease Chronic Myeloid Leukemia (CML). Data pre-specified to be collected in the Advanced Disease CML - AP and Blast Phase/PH+ ALL arms only.

Percentage of Participants With Complete, Major, and Overall Hematologic Response (CHR, MaHR, & OHR) in Advanced Disease Chronic Myeloid Leukemia (AD CML) and Blast Phase CML/Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

Percentage of Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants With Complete Hematologic Response (CHR)

All treated participants with Chronic Phase Chronic Myeloid Leukemia (CP - CML) with MCyR. Data pre-specified to be collected in the Chronic Phase (CP) CML arm only.

Time to Major Cytogenetic Response (MCyR) in Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants

Duration of Major Cytogenetic Response (MCyR) in Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants

Progression-free Survival Among CP CML Participants

All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL

All treated participants with Advanced Disease Chronic Myeloid Leukemia (CML) with CHR or MaHR. Data pre-specified to be collected in the Advanced Disease CML - AP and Blast Phase/PH+ ALL arms only.

Time to Complete and Major Hematologic Response (CHR and MaHR) in Advanced Disease Chronic Myeloid Leukemia (AD CML) and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Participants (Ph+ ALL)

All treated participants with Advanced Disease Chronic Myeloid Leukemia (CML) with CHR. Data pre-specified to be collected in the Advanced Disease CML - AP and Blast Phase/PH+ ALL arms only.

Duration of CHR Among AD CML and Ph+ ALL Participants

All treated participants with Advanced Disease Chronic Myeloid Leukemia (CML) with CHR or NEL or MiHR. Data pre-specified to be collected in the Advanced Disease CML - AP and Blast Phase/PH+ ALL arms only.

Duration of MaHR Among AD CML and Ph+ ALL Participants

Progression-free Survival Among AD CML and Ph+ ALL Participants

Deaths

All-Causality SAEs

Drug-Related SAEs

All-Causality AEs Leading to Discontinuation

Drug-Related AEs leading to Discontinuation

All AEs

Drug-Related AEs

Drug-Related Gr3/4 AEs

Drug-related Fluid Retention-related AEs (FR AE) - Ascites

Drug-related FR AE - Pleural Effusion

Drug-related FR AE - Pulmonary Hypertension

Drug-related FR AE - Oedema Peripheral

Drug-related FR AE - Pericardial Effusion

Drug-related FR AE - Oedema

Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest

Day 1: 0.5 hours postdose

Day 1 : 1 hour postdose

Day 1 : 2 hours postdose

Day 1 : 3 hours postdose

Day 1 : 4 hours postdose

Day 1 : 5 hours postdose

Day 1 : 6 hours postdose

Day 1 : 8 hours postdose

Day 1 : 12 hours postdose

Day 1 : 24 hours postdose

Day 6: 0 hours postdose

Day 7: 0 hours postdose

Day 8: 0 hours postdose

Day 8: 0.5 hours postdose

Day 8: 1 hours postdose

Day 8: 2 hours postdose

Day 8: 3 hours postdose

Day 8: 4 hours postdose

Day 8: 5 hours postdose

Day 8: 6 hours postdose

Day 8: 8 hours postdose

Day 8: 12 hours postdose

Participants with AP CML or Ph+ ALL treated with 70 mg dasatinib BID

70 mg BID

Participants with CP CML treated with dasatinib 100 mg QD

100 mg QD

All treated participants with evaluable PK data. Data collection pre-specified by treatment dosage.

Spots Global Cancer Trial Database for Dasatinib in Imatinib Resistant/Intolerant Chinese CML (Chronic and Advanced Phase) Subjects

Trial Identification

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Study Description

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