Clinical Trial of BP1001 (L-Grb-2 Antisense Oligonucleotide) in CML, AML, ALL & MDS
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.
Recurrent Adult Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Ph1 Positive CML
Drug: BP1001 in combination with LDAC
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Clinical Trial to Study the Safety, Pharmacokinetics, and Efficacy of BP1001 (L-Grb-2 Antisense Oligonucleotide) in Patients With Refractory or Relapsed Acute Myeloid Leukemia, Philadelphia Chromosome Positive Chronic Myelogenous Leukemia, or Acute Lymphoblastic Leukemia, and Myelodysplastic Syndrome|
- Safety of BP1001 [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]Evaluate toxicity, tolerance, and MTD of escalating doses of BP1001
- Safety of BP1001 in combination with LDAC [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]Evaluate safety and toxicity of the combination of BP1001 and concurrent LDAC using non-hematologic and hematologic measures per NCI CTCAE criteria.
- Optimal biologically active dose [ Time Frame: 30 days ] [ Designated as safety issue: No ]Determine the optimal biologically active dose of BP1001 defined as a 50% reduction in Grb-2 expression in circulating leukemia cells
- In vivo pharmacokinetics [ Time Frame: 30 days ] [ Designated as safety issue: No ]Evaluate the in vivo PK of BP1001 in all subjects using plasma and urine to compute half life and elimination
- Correlate PK data with historical experience [ Time Frame: 30 days ] [ Designated as safety issue: No ]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
|Study Start Date:||June 2010|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Subjects are treated with open-label study drug (BP1001) in a dose-escalation model.
Study drug (BP1001) is constituted in normal saline, administered by IV on twice weekly for 28 days.
Experimental: BP1001 in combination with LDAC
AML subjects are treated with open-label escalating study drug (BP1001) in combination with low dose ara-C (LDAC)
Drug: BP1001 in combination with LDAC
Study drug (BP1001) is constituted in normal saline, administered by IV twice weekly for 28 days. Low dose ara-C (LDAC) is self administered twice daily for 10 consecutive days during the 28 day cycle.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01159028
|Contact: Jorge Cortes, MDfirstname.lastname@example.org|
|United States, Texas|
|M. D. Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator: Jorge Cortes, MD|
|Study Chair:||Jorge Cortes, MD||M.D. Anderson Cancer Center|