A Clinical Trial of BP1002 in Patients With Advanced Lymphoid Malignancies

Mantle Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04072458
• Other study ID #: BP1002-101-Lymph
• Status: Recruiting
• Phase: Phase 1
• Start date: November 5, 2020
• Est. completion date: January 2026

Study information

• Verified date: February 2024
• Source: Bio-Path Holdings, Inc.
• Contact: Michael Hickey
• Phone: 832-742-1361
• Email: mhickey[@]biopathholdings.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: January 2026
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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.

Locations

Country	Name	City	State
United States	Georgia Cancer Center	Augusta	Georgia
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	MD Anderson Cancer Research Center	Houston	Texas
United States	Sarah Cannon Research Institute/Tennesee Oncology	Nashville	Tennessee
United States	New York Medical College / Westchester Medical Center	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Bio-Path Holdings, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	Identify Dose Limiting Toxicity (DLT) of BP1002	Identify DLT of BP1002 using non-hematologic and hematologic measures per NCI CTCAE criteria	30 days
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Determine plasma pharmacokinetics (PK) of BP1002 using volume of distribution	Evaluate in vivo PK of BP1002 volume of distribution (Vd)	30 days
Primary	Determine plasma pharmacokinetics (PK) of BP1002 using elimination rate constant	Evaluate in vivo PK of BP1002 elimination rate constant	30 days
Primary	Determine half-life plasma pharmacokinetics (PK) of BP1002	Evaluate in vivo PK of BP1002 half-life (t1/2)	30 days
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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