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®)
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 121
- Locations
- 4
- Primary Endpoint
- Percentage of Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants With Major Cytogenetic Response (MCyR)
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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:
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0-2
- •Adequate hepatic function
- •Adequate renal function
- •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
Arms & Interventions
1
Intervention: Dasatinib (Drug)
Outcomes
Primary Outcomes
Percentage of Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants With Major Cytogenetic Response (MCyR)
Time Frame: From first dose up to approximately 12 months of follow up after dasatinib treatment (data cut-off date: 18-Jun-2010)
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 \[BM\].
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)
Time Frame: From first dose up to approximately 12 months of follow up after dasatinib treatment (data cut-off date: 18-Jun-2010)
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)
Secondary Outcomes
- Percentage of Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants With Complete Hematologic Response (CHR)(From first dose up to approximately 12 months of follow up after dasatinib treatment (data cut-off date: 18-Jun-2010))
- Time to Major Cytogenetic Response (MCyR) in Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants(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]))
- Duration of Major Cytogenetic Response (MCyR) in Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants(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]))
- Progression-free Survival Among CP CML Participants(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]))
- 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)(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]))
- Duration of CHR Among AD CML and Ph+ ALL Participants(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]))
- Duration of MaHR Among AD CML and Ph+ ALL Participants(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]))
- Progression-free Survival Among AD CML and Ph+ ALL Participants(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]))
- Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest(From first dose to 30 days after last dose. (Up to approximately 161 months))
- Mean Dasatinib Plasma Concentrations(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),)
- Mean Maximum Concentration (Cmax) of Dasatinib Following 70 mg BID and 100 QD Dose Administration(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))
- Mean (Tmax) and (T-Half) of Dasatinib Following 70 mg BID and 100 QD Dose Administration(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))
- Mean (AUC[0-T]), (AUC[INF]), and (AUC[TAU])of Dasatinib Following 70 mg BID and 100 QD Dose Administration(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))
- Mean Oral Clearance (CLo) of Dasatinib Following 70 mg BID and 100 QD Dose Administration(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))
- Mean Apparent Volume of Distribution (Vz/F) of Dasatinib Following 70 mg BID and 100 QD Dose Administration(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))