Clinical Trial of BP1001 (Liposomal Grb2 Antisense Oligonucleotide) in Combination With Dasatinib in Patients With Ph + CML Who Have Failed TKI, Ph+ AML, Ph+ MDS

Acute Myeloid Leukemia Clinical Trial

Official title: 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)

Status Withdrawn

Clinical Trial Summary

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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Chronic Myelogenous Leukemia, Ph1-Positive
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

• NCT number: NCT02923986
• Study type: Interventional
• Source: Bio-Path Holdings, Inc.
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: September 1, 2017
• Completion date: May 27, 2020