Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Clinical Trial of BP1002 in Patients With Advanced Lymphoid Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04072458
Recruitment Status : Recruiting
First Posted : August 28, 2019
Last Update Posted : January 27, 2021
Sponsor:
Information provided by (Responsible Party):
Bio-Path Holdings, Inc.

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.

Condition or disease Intervention/treatment Phase
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 Drug: L-Bcl-2 antisense oligonucleotide Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 5, 2020
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : August 2022


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 Name: BP1002




Primary Outcome Measures :
  1. Identify Dose Limiting Toxicity (DLT) of BP1002 [ Time Frame: 30 days ]
    Identify DLT of BP1002 using non-hematologic and hematologic measures per NCI CTCAE criteria

  2. Identify and grade treatment-emergent adverse events (TEAE) of escalating doses of BP1002 [ Time Frame: 30 days ]
    Identify TEAE of BP1002 using non-hematologic and hematologic measures per NCI CTCAE criteria

  3. Identify and grade treatment-emergent laboratory abnormalities of escalating doses of BP1002 by identification and grading of [ Time Frame: 30 days ]
    Identify and grade treatment-emergent laboratory abnormalities of BP1002 using non-hematologic and hematologic measures per NCI CTCAE criteria

  4. Identify conduction and rhythm changes (treatment emergent QTc elevations or other treatment emergent changes in EKG intervals) of escalating doses of BP1002 [ Time Frame: 30 days ]
    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)

  5. Recommended Phase 2 dose (RP2D) of BP1002 [ Time Frame: 210 days ]
    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.

  6. Determine plasma pharmacokinetics (PK) of BP1002 using maximum plasma drug concentration [ Time Frame: 30 days ]
    Evaluate in vivo PK of BP1002 using maximum plasma drug concentration (Cmax)

  7. Determine plasma pharmacokinetics (PK) of BP1002 using volume of distribution [ Time Frame: 30 days ]
    Evaluate in vivo PK of BP1002 volume of distribution (Vd)

  8. Determine plasma pharmacokinetics (PK) of BP1002 using elimination rate constant [ Time Frame: 30 days ]
    Evaluate in vivo PK of BP1002 elimination rate constant

  9. Determine half-life plasma pharmacokinetics (PK) of BP1002 [ Time Frame: 30 days ]
    Evaluate in vivo PK of BP1002 half-life (t1/2)

  10. Determine pharmacokinetics (PK) of BP1002 [ Time Frame: 30 days ]
    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


Secondary Outcome Measures :
  1. Determine evidence of tumor response by bone marrow aspirate [ Time Frame: 30 days ]
    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)

  2. Determine evidence of tumor response by Complete Blood Count (CBC) [ Time Frame: 30 days ]
    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)

  3. Determine estimates for time to progression (TTP) [ Time Frame: 30 days ]
    Measured from treatment start date to date of progression by CBC and/or bone marrow aspirate

  4. Determine estimates for progression-free survival (PFS) [ Time Frame: 30 days ]
    Measured from treatment start date to date of progression or death by CBC and/or bone marrow aspirate

  5. Determine estimates for event-free survival (EFS) [ Time Frame: 30 days ]
    Measured from treatment start date to date of progression, death, or change in therapy by CBC and/or bone marrow aspirate

  6. Activity of BP1002 on Bcl-2 expression in tumor samples [ Time Frame: 30 days ]
    Flow cytometric assays to determine the effects of BP1002 on Bcl-2 protein expression using patient blood samples


Other Outcome Measures:
  1. Exploratory objective to correlate treatment response with cytogenetic characteristics [ Time Frame: 30 days ]
    Flow cytometric assays to determine the effects of BP1002 on Bcl-2 protein expression

  2. Exploratory objective to correlate treatment response with molecular characteristics [ Time Frame: 30 days ]
    Flow cytometric assays to determine the effects of BP1002 on Bcl-2 protein expression



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04072458


Contacts
Layout table for location contacts
Contact: Michael Hickey 832-742-1361 mhickey@biopathholdings.com

Locations
Layout table for location information
United States, Georgia
Georgia Cancer Center Recruiting
Augusta, Georgia, United States, 30912
Contact: Julie Stiefel    706-721-0734    jstiefel@augusta.edu   
Principal Investigator: Locke J Bryan, MD         
United States, Tennessee
Sarah Cannon Research Institute/Tennesee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Matthew Price    615-524-4100    matthew.price@sarahcannon.com   
Principal Investigator: Ian W Flinn, MD, PhD         
United States, Texas
MD Anderson Cancer Research Center Recruiting
Houston, Texas, United States, 77030
Contact: Philip Thompson, MB, BS    713-792-7430    PAThompson2@mdanderson.org   
Principal Investigator: Philip Thompson, MB, BS         
Sponsors and Collaborators
Bio-Path Holdings, Inc.
Layout table for additonal information
Responsible Party: Bio-Path Holdings, Inc.
ClinicalTrials.gov Identifier: NCT04072458    
Other Study ID Numbers: BP1002-101-Lymph
First Posted: August 28, 2019    Key Record Dates
Last Update Posted: January 27, 2021
Last Verified: January 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, T-Cell
Waldenstrom Macroglobulinemia
Lymphoma, T-Cell, Peripheral
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia
Leukemia, B-Cell
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders