Clinical Trial of BP1001 (L-Grb-2 Antisense Oligonucleotide) in CML, AML, ALL & MDS

Phase 1

Completed

• Conditions: Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Ph1 Positive CML; Myelodysplastic Syndrome
• Interventions: Drug: BP1001; Drug: BP1001 in combination with LDAC

• Registration Number: NCT01159028
• Lead Sponsor: Bio-Path Holdings, Inc.

Brief Summary

The first goal of this clinical research study is to find the highest safe dose of BP1001, a liposomal Growth Factor Receptor Bound Protein-2 antisense oligodeoxynucleotide (L-Grb2 AS), for patients with Philadelphia Chromosome positive CML, AML, ALL and MDS. The response of the leukemia to this treatment will also be studied. The second goal of this clinical research study is to evaluate the safety and toxicity of the combination of BP1001 and concurrent low-dose ara-C (LDAC) in patients with AML.

Detailed Description

The Philadelphia Chromosome is an unusual genetic trait found in 90-95% of patients with CML and approximately 20-25% of patients with ALL. The protein created by this unusual trait causes normal cells within the body to become cancer cells, and then causes these cells to grow and divide at a rapid rate. Researchers think that the protein "Growth Factor Receptor Bound Protein-2 (Grb-2)" plays an important role in the rapid growth of leukemic cells. 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.

Up to 60 patients are expected to be enrolled on this study.

Part A: Dose escalation: Each cohort will receive BP1001 at a dose higher than the previous group.

Part B: Dose-expansion Cohorts: Subjects with relapsed or refractory AML will receive escalating doses of BP1001 concurrently with fixed low-dose ara-C (LDAC)

The study drug is an antisense molecule complementary to the messenger RNA (mRNA) code for the cell's expression of the protein Grb-2. The study drug is incorporated into lipid (fat) particles known as liposomes. This incorporation process is part of the manufacturing process and is done before the study drug is administered. The liposomes (which carry the study drug) will be administered intravenously twice a week for 28 days. Subjects enrolled in Part B of the study will receive study drug twice a week for 28 days concurrently with low dose ara-C, self administered twice daily for 10 consecutive days.

Study Timeline

• Study Start: 2010-06
• Study First Submitted: 2010-07-07
• Study First Submitted QC: 2010-07-08
• Study First Posted: 2010-07-09
• Primary Completion: 2017-03-30
• Study Completion: 2017-03-30
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-26
• Last Update Posted: 2020-05-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BP1001	BP1001	Subjects are treated with open-label study drug (BP1001) in a dose-escalation model.
BP1001 in combination with LDAC	BP1001 in combination with LDAC	AML subjects are treated with open-label escalating study drug (BP1001) in combination with low dose ara-C (LDAC)

Primary Outcome Measures

Name	Time	Method
Safety of BP1001	30 days	Evaluate toxicity, tolerance, and MTD of escalating doses of BP1001
Safety of BP1001 in combination with LDAC	30 days	Evaluate safety and toxicity of the combination of BP1001 and concurrent LDAC using non-hematologic and hematologic measures per NCI CTCAE criteria.

Secondary Outcome Measures

Name	Time	Method
In vivo pharmacokinetics	30 days	Evaluate the in vivo PK of BP1001 in all subjects using plasma and urine to compute half life and elimination
Optimal biologically active dose	30 days	Determine the optimal biologically active dose of BP1001 defined as a 50% reduction in Grb-2 expression in circulating leukemia cells
Correlate PK data with historical experience	30 days	Correlate the in vivo PK data with historical experience to demonstrate the liposomal delivery performs as expected for all subjects by comparing PK data (half life and elimination) obtained from each subject with historical experience

Trial Locations

Locations (1)

M. D. Anderson Cancer Center; 🇺🇸 Houston, Texas, United States