This study evaluates the safety, pharmacokinetics, and efficacy of BP1002 (L-Bcl-2) antisense oligonucleotide in patients with advanced lymphoid malignancies. Up to 12 evaluable patients with a diagnosis of relapsed or refractory lymphoid malignancies are expected to participate.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
There will be 2 planned dose levels, 20, and 40 mg/m\^2. Successive cohorts of eligible patients with will be treated with BP1002. BP1002 is given as an intravenous infusion, twice weekly, as 8 doses per 28-day cycle. Cycles may be repeated every 4 weeks.
Georgia Cancer Center
Augusta, Georgia, United States
New York Medical College / Westchester Medical Center
Valhalla, New York, United States
Sarah Cannon Research Institute/Tennesee Oncology
Nashville, Tennessee, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
MD Anderson Cancer Research Center
Houston, Texas, United States
Identify Dose Limiting Toxicity (DLT) of BP1002
Identify DLT of BP1002 using non-hematologic and hematologic measures per NCI CTCAE criteria
Time frame: 30 days
Identify and grade treatment-emergent adverse events (TEAE) of escalating doses of BP1002
Identify TEAE of BP1002 using non-hematologic and hematologic measures per NCI CTCAE criteria
Time frame: 30 days
Identify and grade treatment-emergent laboratory abnormalities of escalating doses of BP1002 by identification and grading of
Identify and grade treatment-emergent laboratory abnormalities of BP1002 using non-hematologic and hematologic measures per NCI CTCAE criteria
Time frame: 30 days
Identify conduction and rhythm changes (treatment emergent QTc elevations or other treatment emergent changes in EKG intervals) of escalating doses of BP1002
Collection of 12-lead EKGs at defined intervals to identify conduction and rhythm changes (treatment emergent QTc elevations or other treatment emergent changes in EKG intervals)
Time frame: 30 days
Recommended Phase 2 dose (RP2D) of BP1002
Determine RP2D by evaluating Maximally Tolerated Dose (MTD) data: Any Dose Limiting Toxicity (DLT) observed will trigger an expansion of a cohort from 3 to 6 patients. A second DLT at any dose level will identify the Maximum Dose. The dose below that will be the MTD.
Time frame: 210 days
Determine plasma pharmacokinetics (PK) of BP1002 using maximum plasma drug concentration
Evaluate in vivo PK of BP1002 using maximum plasma drug concentration (Cmax)
Time frame: 30 days
Determine plasma pharmacokinetics (PK) of BP1002 using volume of distribution
Evaluate in vivo PK of BP1002 volume of distribution (Vd)
Time frame: 30 days
Determine plasma pharmacokinetics (PK) of BP1002 using elimination rate constant
Evaluate in vivo PK of BP1002 elimination rate constant
Time frame: 30 days
Determine half-life plasma pharmacokinetics (PK) of BP1002
Evaluate in vivo PK of BP1002 half-life (t1/2)
Time frame: 30 days
Determine pharmacokinetics (PK) of BP1002
12-lead EKG assessments will be collected and analyzed for conduction and rhythm changes (treatment emergent QTc elevations or other treatment emergent changes in EKG intervals) from those the EKG obtained immediately before the first BP1002 dose, and after BP1002 dose, and will mirror the time points used to collect the plasma PK assessments
Time frame: 30 days
Determine evidence of tumor response by bone marrow aspirate
Assess tumor response by evaluating bone marrow aspirate to determine complete response (CR), partial response (PR), or minor response (MR) using appropriate uniform response criteria as published by Response Evaluation Criteria in Lymphoma (RECIL) 2017, CLL guidelines, and International Workshop on Waldenström's Macroglobulinemia (IWWM 6th)
Time frame: 30 days
Determine evidence of tumor response by Complete Blood Count (CBC)
Assess tumor response by evaluating CBC measurements to determine complete response (CR), partial response (PR), or minor response (MR) using appropriate uniform response criteria as published by Response Evaluation Criteria in Lymphoma (RECIL) 2017, CLL guidelines, and International Workshop on Waldenström's Macroglobulinemia (IWWM 6th)
Time frame: 30 days
Determine estimates for time to progression (TTP)
Measured from treatment start date to date of progression by CBC and/or bone marrow aspirate
Time frame: 30 days
Determine estimates for progression-free survival (PFS)
Measured from treatment start date to date of progression or death by CBC and/or bone marrow aspirate
Time frame: 30 days
Determine estimates for event-free survival (EFS)
Measured from treatment start date to date of progression, death, or change in therapy by CBC and/or bone marrow aspirate
Time frame: 30 days
Activity of BP1002 on Bcl-2 expression in tumor samples
Flow cytometric assays to determine the effects of BP1002 on Bcl-2 protein expression using patient blood samples
Time frame: 30 days
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