Clinical trial NCT00529763: Dasatinib in Imatinib Resistant/Intolerant Chinese CML (Chronic and Advanced Phase) Subjects
Official title: 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®)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: Chronic Phase, Advanced Phase chronic myeloid leukemia
Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2007-09-14
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Signed Written Informed Consent
* Men and women, ages 18 years of age or older
* Subjects with Chronic Phase (CP) or Advanced Disease (AD) chronic myeloid leukemia (CML)/Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
* Subjects resistant/intolerant to imatinib
* Subjects presenting:

  1. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0-2
  2. Adequate hepatic function
  3. Adequate renal function
  4. Sodium, Potassium, Magnesium, Phosphorus, Calcium higher or equal than the lower limit of normal range

Exclusion Criteria:

* Women of child bearing potential who are not using adequate birth control
* Women who are pregnant or breastfeeding
* Subjects eligible for stem cell transplantation
* Serious uncontrolled medical disorder or active infection
* Uncontrolled or significant cardiovascular disease
* Concurrent incurable malignancy other than CML
* Subjects who received imatinib, interferon, cytarabine within 7 days or other antineoplastic agents other than hydroxyurea within 14 days before dasatinib, Dasatinib in the past
* History of significant bleeding unrelated to CML

Primary outcomes:
measure: Percentage of Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants With Major Cytogenetic Response (MCyR)
timeFrame: From first dose up to approximately 12 months of follow up after dasatinib treatment (data cut-off date: 18-Jun-2010)
measure: 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)
timeFrame: From first dose up to approximately 12 months of follow up after dasatinib treatment (data cut-off date: 18-Jun-2010)
Secondary outcomes:
measure: Percentage of Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants With Complete Hematologic Response (CHR)
timeFrame: From first dose up to approximately 12 months of follow up after dasatinib treatment (data cut-off date: 18-Jun-2010)
measure: Time to Major Cytogenetic Response (MCyR) in Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants
timeFrame: From first dose up to the day criteria were first met for CCyR or PCyR, whichever occurred first. (Up to approximately 12 months of follow up after dasatinib treatment [data cut-off date: 18-Jun-2010])
measure: Duration of Major Cytogenetic Response (MCyR) in Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants
timeFrame: From first dose until the date of progression or death. (Up to approximately 12 months of follow up after dasatinib treatment [data cut-off date: 18-Jun-2010])
measure: Progression-free Survival Among CP CML Participants
timeFrame: From first dosing date until the time progressive disease (PD) is first documented. (Up to approximately 12 months of follow up after dasatinib treatment [data cut-off date: 18-Jun-2010])
measure: 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)
timeFrame: From first dose of Dasatinib until the first day CHR criteria are met (for all confirmed responses). (Up to approximately 12 months of follow up after dasatinib treatment [data cut-off date: 18-Jun-2010])
measure: Duration of CHR Among AD CML and Ph+ ALL Participants
timeFrame: From first dose until the date of disease progression (PD) or death. (Up to approximately 12 months of follow up after dasatinib treatment [data cut-off date: 18-Jun-2010])
measure: Duration of MaHR Among AD CML and Ph+ ALL Participants
timeFrame: From first dose until the date of disease progression (PD) or death. (Up to approximately 12 months of follow up after dasatinib treatment [data cut-off date: 18-Jun-2010])
measure: Progression-free Survival Among AD CML and Ph+ ALL Participants
timeFrame: From first dose until the time progressive disease (PD) is first documented. (Up to approximately 12 months of follow up after dasatinib treatment [data cut-off date: 18-Jun-2010])
measure: Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest
timeFrame: From first dose to 30 days after last dose. (Up to approximately 161 months)
measure: Mean Dasatinib Plasma Concentrations
timeFrame: Day 1 (0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours postdose), Days 6 and 7 (0 hours postdose), Day 8 (0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hours postdose),
measure: Mean Maximum Concentration (Cmax) of Dasatinib Following 70 mg BID and 100 QD Dose Administration
timeFrame: Day 1 (0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours postdose), Day 8 (0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hours postdose)
measure: Mean (Tmax) and (T-Half) of Dasatinib Following 70 mg BID and 100 QD Dose Administration
timeFrame: Day 1 (0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours postdose), Day 8 (0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hours postdose)
measure: Mean (AUC[0-T]), (AUC[INF]), and (AUC[TAU])of Dasatinib Following 70 mg BID and 100 QD Dose Administration
timeFrame: Day 1 (0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours postdose), Day 8 (0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hours postdose)
measure: Mean Oral Clearance (CLo) of Dasatinib Following 70 mg BID and 100 QD Dose Administration
timeFrame: Day 1 (0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours postdose), Day 8 (0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hours postdose)
measure: Mean Apparent Volume of Distribution (Vz/F) of Dasatinib Following 70 mg BID and 100 QD Dose Administration
timeFrame: Day 1 (0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours postdose), Day 8 (0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hours postdose)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Fuzhou
country: China
facility: Local Institution - 0004
state: Fujian
city: Fuzhou
country: China
facility: Local Institution
state: Fujian
city: Guangzhou
country: China
facility: Local Institution
state: Guangdong
city: Nanjing
country: China
facility: Local Institution
state: Jiangsu
city: Suzhou
country: China
facility: Local Institution - 0008
state: Jiangsu
city: Suzhou
country: China
facility: Local Institution
state: Jiangsu
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Chengdou
country: China
facility: Local Institution
state: Sichuan
city: Chengdu
country: China
facility: Local Institution
state: Sichuan
city: Tianjin
country: China
facility: Local Institution
state: Tianjin
city: Hangzhou
country: China
facility: Local Institution - 0009
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution
state: Zhejiang
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: