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
- Conditions
- Acute Myeloid LeukemiaMyelodysplastic SyndromeChronic Myelogenous Leukemia, Ph1-Positive
- Interventions
- Registration Number
- NCT02923986
- Lead Sponsor
- Bio-Path Holdings, Inc.
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BP1001 (fixed dose) + Dasatinib Dasatinib Phase IIa: BP1001 (fixed dose based on Phase 1b) in combination with Das BP1001 (varying dose) + Dasatinib BP1001 (varying dose) Phase 1b: BP1001 (varying dose levels) in combination with Das BP1001 (varying dose) + Dasatinib Dasatinib Phase 1b: BP1001 (varying dose levels) in combination with Das BP1001 (fixed dose) + Dasatinib BP1001 (fixed dose) Phase IIa: BP1001 (fixed dose based on Phase 1b) in combination with Das
- Primary Outcome Measures
Name Time Method Efficacy of the combination of BP1001 and Das using hematologic response by bone marrow aspirate or biopsy and complete blood counts 240 days Phase IIa portion of the study: Assess the efficacy of the combination of BP1001 and Das
Dose Limiting Toxicity of BP1001 using non-hematologic and hematologic parameters per NCI CTCAE criteria 240 days Phase 1b portion of the study: Determine the dose limiting toxicity of BP1001 in combination with Das
Maximum Tolerated Dose of BP1001 using non-hematologic and hematologic parameters per NCI CTCAE criteria 240 days Phase 1b portion of the study: Determine the maximum tolerated dose of BP1001 in combination with Das
Efficacy of the combination of BP1001 and Das using cytogenetic response (karyotyping) by bone marrow aspirate or biopsy 240 days Phase IIa portion of the study: Assess the efficacy of the combination of BP1001 and Das
Efficacy of the combination of BP1001 and Das using molecular response (PCR) by bone marrow aspirate or biopsy 240 days Phase IIa portion of the study: Assess the efficacy of the combination of BP1001 and Das
- Secondary Outcome Measures
Name Time Method 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 Determine whether the combination of BP1001 and Das provides greater efficacy (Hematologic Response) than Das alone (by historical comparison)
Duration of Response using cytogenetic response (karyotyping) using bone marrow biopsy or aspirate from day of response to day of disease progression 30 days Assess duration of response from day of response to day of disease progression
Overall Survival from date of study entry to study closure 240 days Assess overall survival from date of study entry to study closure
Time to Response using hematologic response using bone marrow biopsy or aspirate and complete blood counts 30 days Assess time to response from administration of BP1001 + Das to hematologic response
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 Assess duration of response from day of response to day of disease progression
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 Determine whether the combination of BP1001 and Das provides greater efficacy (Molecular Response) than Das alone (by historical comparison)
Time to Response using molecular response (PCR) using bone marrow biopsy or aspirate 30 days Assess time to response from administration of BP1001 + Das to molecular response
Duration of Response using molecular response (PCR) using bone marrow biopsy or aspirate from day of response to day of disease progression 30 days Assess duration of response from day of response to day of disease progression
Safety of BP1001 in combination with Das using non-hematologic and hematologic parameters per NCI CTCAE criteria 30 days Evaluate Safety of BP1001 in combination with Das
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 Determine whether the combination of BP1001 and Das provides greater efficacy (Cytogenetic Response) than Das alone (by historical comparison)
In vivo PK using plasma to compute half life and elimination 30 days Evaluate in vivo PK of BP1001 when given alone and in combination with Das
Time to Response using cytogenetic response (karyotyping) using bone marrow biopsy or aspirate 30 days Assess time to response from administration of BP1001 + Das to cytogenetic response
Trial Locations
- Locations (1)
The University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States