A Phase Ib/IIa Single-arm, Open-label Clinical Trial to Evaluate the Safety, Pharmacokinetics, and Efficacy of BP1001 (a Liposomal Grb2 Antisense Oligonucleotide) in Combination With Dasatinib in Patients 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)

Brief Summary

Detailed Description

The Grb2 gene has been mapped to the human chromosome region 17q22-qter, a region that is duplicated in leukemias and solid tumors, which may result in an increased copy number of the Grb2 gene product. As Grb2 is important for the transformation of murine hematopoietic cells, and the proliferation of human leukemia cells that express high levels of oncogenic tyrosine kinases, inhibition of Grb2 may have a significant impact on the natural history of leukemias. The study drug (BP1001) may be able to inhibit the cells from making Grb-2. Researchers hope that without this protein, the leukemia cells will die. Researchers hope that the combination of BP1001 and Das will provide a benefit to Ph+ CML patients, including chronic phase patients who have failed initial TKI therapy, accelerated or blast phase Ph+ AML, and high-risk Ph+ MDS patients. This is a Phase Ib/IIa, multicenter, study of BP1001 in combination with Das in participants with Ph+ CML, including chronic phase patients who have failed initial TKI therapy, accelerated or blast phase Ph+ AML, and high-risk Ph+ MDS. This is a Phase Ib/IIa, multicenter, study of BP1001 in combination with dasatinib in participants with Ph+ CML who are in chronic phase who have failed initial TKI therapy, accelerated or blast phase, Ph+ AML or high-risk Ph+ MDS. This trial will utilize a single arm, open label design to assess the safety profile, DLT, MTD, PK, and efficacy of BP1001 in combination with dasatinib. The Phase Ib study employs an open-label, sequential, dose-escalation design to assess safety, tolerability and toxicity, tumor response and anti-leukemic activity. A standard "3+3" design will be used in which successive cohorts of patients are being treated with BP1001 at the MTD (or highest tested dose \[HTD\] if the MTD is not defined) and 1 level below the MTD (or HTD) in combination with a fixed dose of dasatinib to characterize safety and biological effect, as well as identify the recommended Phase IIa dose. Up to 6 evaluable participants are expected to participate in the Phase Ib part of the study and up to 40 evaluable participants are expected to participate in the Phase IIa part of the study.

Primary Outcomes

Secondary Outcomes

• Time to Response using hematologic response using bone marrow biopsy or aspirate and complete blood counts(30 days)
• 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(30 days)
• 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(240 days)
• Time to Response using molecular response (PCR) using bone marrow biopsy or aspirate(30 days)
• Duration of Response using molecular response (PCR) using bone marrow biopsy or aspirate from day of response to day of disease progression(30 days)
• Safety of BP1001 in combination with Das using non-hematologic and hematologic parameters per NCI CTCAE criteria(30 days)
• 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(240 days)
• In vivo PK using plasma to compute half life and elimination(30 days)
• Time to Response using cytogenetic response (karyotyping) using bone marrow biopsy or aspirate(30 days)
• 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(240 days)
• Duration of Response using cytogenetic response (karyotyping) using bone marrow biopsy or aspirate from day of response to day of disease progression(30 days)
• Overall Survival from date of study entry to study closure(240 days)