A Clinical Trial of BP1002 in Patients With Advanced Lymphoid Malignancies

A Phase 1 Clinical Trial to Study the Safety, Pharmacokinetics, and Efficacy of BP1002 (L-Bcl-2) Antisense Oligonucleotide in Patients With Advanced Lymphoid Malignancies

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 Overview

• Status: Recruiting
• Conditions: Follicular Lymphoma; Hodgkin Lymphoma; Waldenstrom Macroglobulinemia; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL); DLBCL; Cutaneous T-cell Lymphoma (CTCL); Peripheral T-cell Lymphoma (PTCL)
• Intervention / Treatment: Drug: L-Bcl-2 antisense oligonucleotide

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Michael Hickey; Phone Number: 832-742-1361; Email: mhickey@biopathholdings.com

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Recruiting
      • Georgia Cancer Center
      • Contact: Julie Stiefel; Phone Number: 706-721-0734; Email: jstiefel@augusta.edu
      • Principal Investigator: Locke J Bryan, MD
  • New York
    • Valhalla, New York, United States, 10595
      • Recruiting
      • New York Medical College / Westchester Medical Center
      • Contact: Allyson Pulsoni; Phone Number: 914-493-6610; Email: allyson.pulsoni@wmchealth.org
      • Contact: Karen Seiter, MD; Email: karen_seiter@nymc.edu
      • Principal Investigator: Karen Seiter, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Terminated
      • Sarah Cannon Research Institute/Tennesee Oncology
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
      • Contact: Ryan Sabu; Phone Number: 214-645-9883; Email: Ryan.Sabu@utsouthwestern.edu
      • Principal Investigator: Praveen Ramakrishnan, MD
    • Houston, Texas, United States, 77030
      • Terminated
      • MD Anderson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults ≥18 years of age
2. Patient has a life expectancy ≥ 3 month

3. 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

4. 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
5. 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
6. Therapy means at least three front lines of therapy including Hematopoeitic Stem Cell Transplant (HSCT and/or Chimeric Antigen Receptor (CAR) T cells, when applicable
7. Females must be of non-childbearing potential, surgically sterile, postmenopausal, or practice adequate methods of contraception during the study
8. Males must agree to use an adequate method of contraception during the study
9. Eastern Cooperative Oncology Group (ECOG) Performance score of 0, 1, or 2

10. Adequate hepatic and renal functions as defined by:

    • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 times the upper limit of normal (ULN); and
    • Total bilirubin ≤1.5 times ULN; and

    • Estimated glomerular filtration rate (eGFR) of at least 50ml/min. These estimations can be calculated using the following methods:

      • Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation
      • Cockcroft Gault equation
      • Modification of Diet in Renal Disease (MDRD study equation)
      • Creatinine clearance estimated by 24-hr urine collection for creatinine clearance
11. Recovered from the effects of any prior surgery, radiotherapy, or antineoplastic treatment (with the exception of alopecia), based on Investigator assessment
12. Willing and able to provide written informed consent

Exclusion Criteria:

1. 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
2. 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
3. Patient eligible for high dose chemotherapy and autologous stem cell transplant
4. Indolent non-Hodgkin lymphoma (iNHL)

5. 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

6. Receipt of any anti-cancer therapy within 14 days prior to Cycle 1 Day 1 (C1D1)
7. Uncontrolled active, untreated, or progressive infection
8. Receipt of any investigational agent or on study treatment within 30 days prior to C1D1
9. 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
10. 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
11. 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)
12. 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)
13. 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
14. Uncontrolled seizure disorder
15. Unable or unwilling to communicate or cooperate with the Investigator or follow the protocol for any reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BP1002 monotherapy; 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; 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.; Other Names: BP1002

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Determine half-life plasma pharmacokinetics (PK) of BP1002	Evaluate in vivo PK of BP1002 half-life (t1/2)	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 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	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	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	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	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	30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory objective to correlate treatment response with cytogenetic characteristics	Flow cytometric assays to determine the effects of BP1002 on Bcl-2 protein expression	30 days
Exploratory objective to correlate treatment response with molecular characteristics	Flow cytometric assays to determine the effects of BP1002 on Bcl-2 protein expression	30 days

Collaborators and Investigators

• Sponsor: Bio-Path Holdings, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2020
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: August 23, 2019
• First Submitted That Met QC Criteria: August 26, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Disease Attributes; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Leukemia, Lymphoid; Leukemia; Leukemia, B-Cell; Chronic Disease; Lymphoma; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous
• Other Study ID Numbers: BP1002-101-Lymph

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No