A Clinical Trial of BP1002 in Patients With Advanced Lymphoid Malignancies

NCT04072458 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BP1002-101-Lymph
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Mantle Cell Lymphoma; Peripheral T-cell Lymphoma (PTCL); Cutaneous T-cell Lymphoma (CTCL); Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL); Follicular Lymphoma; Marginal Zone Lymphoma; Hodgkin Lymphoma; Waldenstrom Macroglobulinemia; DLBCL

Outcome Measures

Primary Outcomes (10)

• Identify Dose Limiting Toxicity (DLT) of BP1002

  Identify DLT of BP1002 using non-hematologic and hematologic measures per NCI CTCAE criteria

  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

  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

  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)

  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.

  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)

  30 days

• Determine plasma pharmacokinetics (PK) of BP1002 using volume of distribution

  Evaluate in vivo PK of BP1002 volume of distribution (Vd)

  30 days

• Determine plasma pharmacokinetics (PK) of BP1002 using elimination rate constant

  Evaluate in vivo PK of BP1002 elimination rate constant

  30 days

• Determine half-life plasma pharmacokinetics (PK) of BP1002

  Evaluate in vivo PK of BP1002 half-life (t1/2)

  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

  30 days

Secondary Outcomes (6)

• Determine evidence of tumor response by bone marrow aspirate

  30 days

• Determine evidence of tumor response by Complete Blood Count (CBC)

  30 days

• Determine estimates for time to progression (TTP)

  30 days

• Determine estimates for progression-free survival (PFS)

  30 days

• Determine estimates for event-free survival (EFS)

  30 days

Other Outcomes (2)

• Exploratory objective to correlate treatment response with cytogenetic characteristics

  30 days

• Exploratory objective to correlate treatment response with molecular characteristics

  30 days

Study Arms (1)

BP1002 monotherapy

EXPERIMENTAL

L-Bcl-2 Antisense oligonucleotide (BP1002) is given in a sequential, dose escalation design. Starting dose is 20mg/m\^2.

Drug: L-Bcl-2 antisense oligonucleotide

Interventions

L-Bcl-2 antisense oligonucleotide DRUG

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.

Also known as: BP1002

BP1002 monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥18 years of age
• Patient has a life expectancy ≥ 3 month
• Patient has relapsed or refractory disease Relapsed lymphoma: Relapsed lymphoma is disease that has responded to treatment but then returns.
• Refractory lymphoma: Failure to achieve complete response at the end of therapy or progression within 6 months from completion of therapy
• Included Diseases
• DLBCL, including transformed lymphoma
• Mantle Cell Lymphoma
• PTCL
• CTCL
• CLL/SLL
• Follicular lymphoma
• Marginal zone lymphoma
• Hodgkin lymphoma (both classical and lymphocyte predominant)
• Waldenströms Macroglobulinemia
• Must has failed or is not a candidate for available therapies with reasonable likelihood of clinical benefit, which includes FDA approved products and standard of care regimens

You may not qualify if:

• Active non-hematologic malignancy other than lymphoid malignancies treated with immuno- or chemotherapy within the previous 12 months except active non-melanoma, non-invasive skin cancer will be allowed
• Known, active Central Nervous System (CNS) involvement of disease requiring intrathecal therapy. Note: Patients with a history of CNS disease may be allowed to participate based on at least 1 documented, negative spinal fluid assessment within 28 days prior to Screening
• Patient eligible for high dose chemotherapy and autologous stem cell transplant
• Indolent non-Hodgkin lymphoma (iNHL)
• Patients at high risk of Tumor Lysis Syndrome (TLS)
• a. Bulky disease i. A unidimensional lesion greater than 10 cm and/or b. Lymphocyte count greater than 25,000 per µL
• Receipt of any anti-cancer therapy within 14 days prior to Cycle 1 Day 1 (C1D1)
• Uncontrolled active, untreated, or progressive infection
• Receipt of any investigational agent or on study treatment within 30 days prior to C1D1
• Females who are pregnant, test positive for pregnancy, or are breast-feeding during the Screening period, or intend to become pregnant or breast-feed during the course of the study or within 30 days after last dose of study drug
• Serious intercurrent medical or psychiatric illness which, in the opinion of the Investigator, would interfere with the ability of the participant to complete the study
• Active hepatitis B infection (based on positive surface antigen \[HBsAg\]), hepatitis C infection (based on Hepatitis C Virus (HCV) positive antibody \[HCV Ab\]), or human immunodeficiency virus (HIV-1 or HIV-2, based on positive antibody)
• Presence of concurrent conditions that, in the opinion of the Investigator and/or Medical Monitor, may compromise or interfere with any aspect of study conduct or interpretation of results. This includes, but is not limited to, unstable or uncontrolled angina, New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled and sustained hypertension, clinically significant cardiac dysrhythmia or clinically significant baseline EKG abnormality (e.g., QTcF \>470 msec)
• Within the past 6 months, has had any of the following: myocardial infarction, unstable angina pectoris, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack
• Uncontrolled seizure disorder

Sponsors & Collaborators

• Bio-Path Holdings, Inc.: lead

Study Sites (5)

Georgia Cancer Center

Augusta, Georgia, 30912, United States

Location

New York Medical College / Westchester Medical Center

Valhalla, New York, 10595, United States

Location

Sarah Cannon Research Institute/Tennesee Oncology

Nashville, Tennessee, 37203, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Research Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Hodgkin Disease; Waldenstrom Macroglobulinemia

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2019
• First Posted: August 28, 2019
• Study Start: November 5, 2020
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: February 24, 2025

Record last verified: 2025-02

Locations

US (5)