The primary objective of the Phase Ib study is to determine the dose-limiting toxicity (DLT) and maximal tolerated dose (MTD) of BP1001 in combination with dasatinib in patients with with Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML) including chronic phase patients who have failed initial tyrosine kinase inhibitor (TKI) therapy, accelerated or blast phase, Ph+ Acute Myeloid Leukemia (AML) or High-risk Ph+ Myelodysplastic Syndrome (MDS). The primary objective of the Phase IIa study is to assess the efficacy of the combination of BP1001 and dasatinib in patients with Ph+ CML, Ph+AML, or high-risk Ph+ MDS.
Name: BP1001 (varying dose)
Description: BP1001 (varying dose)Type: DrugBP1001 (varying dose) + Dasatinib
Name: BP1001 (fixed dose)
Description: BP1001 (fixed dose)Type: DrugBP1001 (fixed dose) + Dasatinib
Name: Dasatinib
Description: DasatinibType: DrugBP1001 (fixed dose) + Dasatinib BP1001 (varying dose) + Dasatinib
Description: Phase 1b portion of the study: Determine the dose limiting toxicity of BP1001 in combination with Das
Measure: Dose Limiting Toxicity of BP1001 using non-hematologic and hematologic parameters per NCI CTCAE criteria Time: 240 daysDescription: Phase 1b portion of the study: Determine the maximum tolerated dose of BP1001 in combination with Das
Measure: Maximum Tolerated Dose of BP1001 using non-hematologic and hematologic parameters per NCI CTCAE criteria Time: 240 daysDescription: Phase IIa portion of the study: Assess the efficacy of the combination of BP1001 and Das
Measure: Efficacy of the combination of BP1001 and Das using hematologic response by bone marrow aspirate or biopsy and complete blood counts Time: 240 daysDescription: Phase IIa portion of the study: Assess the efficacy of the combination of BP1001 and Das
Measure: Efficacy of the combination of BP1001 and Das using cytogenetic response (karyotyping) by bone marrow aspirate or biopsy Time: 240 daysDescription: Phase IIa portion of the study: Assess the efficacy of the combination of BP1001 and Das
Measure: Efficacy of the combination of BP1001 and Das using molecular response (PCR) by bone marrow aspirate or biopsy Time: 240 daysDescription: Evaluate Safety of BP1001 in combination with Das
Measure: Safety of BP1001 in combination with Das using non-hematologic and hematologic parameters per NCI CTCAE criteria Time: 30 daysDescription: Determine whether the combination of BP1001 and Das provides greater efficacy (Hematologic Response) than Das alone (by historical comparison)
Measure: Efficacy of the combination of BP1001 and Das using hematologic response by bone marrow aspirate or biopsy and complete blood counts versus Das alone by historical outcome comparison Time: 240 daysDescription: Determine whether the combination of BP1001 and Das provides greater efficacy (Cytogenetic Response) than Das alone (by historical comparison)
Measure: Efficacy of the combination of BP1001 and Das using cytogenetic response (karyotyping) by bone marrow aspirate or biopsy versus Das alone by historical outcome comparison Time: 240 daysDescription: Determine whether the combination of BP1001 and Das provides greater efficacy (Molecular Response) than Das alone (by historical comparison)
Measure: Efficacy of the combination of BP1001 and Das using molecular response (PCR) by bone marrow aspirate or biopsy versus Das alone by historical outcome comparison Time: 240 daysDescription: Evaluate in vivo PK of BP1001 when given alone and in combination with Das
Measure: In vivo PK using plasma to compute half life and elimination Time: 30 daysDescription: Assess time to response from administration of BP1001 + Das to hematologic response
Measure: Time to Response using hematologic response using bone marrow biopsy or aspirate and complete blood counts Time: 30 daysDescription: Assess time to response from administration of BP1001 + Das to cytogenetic response
Measure: Time to Response using cytogenetic response (karyotyping) using bone marrow biopsy or aspirate Time: 30 daysDescription: Assess time to response from administration of BP1001 + Das to molecular response
Measure: Time to Response using molecular response (PCR) using bone marrow biopsy or aspirate Time: 30 daysDescription: Assess duration of response from day of response to day of disease progression
Measure: Duration of Response using hematologic response using bone marrow biopsy or aspirate and complete blood counts from day of response to day of disease progression Time: 30 daysDescription: Assess duration of response from day of response to day of disease progression
Measure: Duration of Response using cytogenetic response (karyotyping) using bone marrow biopsy or aspirate from day of response to day of disease progression Time: 30 daysDescription: Assess duration of response from day of response to day of disease progression
Measure: Duration of Response using molecular response (PCR) using bone marrow biopsy or aspirate from day of response to day of disease progression Time: 30 daysDescription: Assess overall survival from date of study entry to study closure
Measure: Overall Survival from date of study entry to study closure Time: 240 daysAllocation: Non-Randomized
Parallel Assignment
There is one SNP
× 0.74 [if female] x 1.212 [if African American (AA)] - Creatinine clearance estimated by 24-hr urine collection for creatinine clearance 6. Documented Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 7. Recovered from the effects of any prior surgery, radiotherapy, or antineoplastic treatment (with the exception of alopecia), based on Investigator assessment 8. Willing and able to provide written informed consent Exclusion Criteria At the time of Screening, participants who meet any of the following criteria will be excluded from participating in the study: 1. Patients with T315I mutation will not be excluded, but their response will be analyzed separately. --- T315I ---