A Clinical Trial of BP1002 in Patients With Advanced Lymphoid Malignancies

Sponsor

Bio-Path Holdings, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04072458

Collaborator

(none)

Enrollment

Locations

Arm

37.8

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Anticipated 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 :

Nov 5, 2020

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Identify Dose Limiting Toxicity (DLT) of BP1002 [30 days]
Identify DLT of BP1002 using non-hematologic and hematologic measures per NCI CTCAE criteria
Identify and grade treatment-emergent adverse events (TEAE) of escalating doses of BP1002 [30 days]
Identify TEAE of BP1002 using non-hematologic and hematologic measures per NCI CTCAE criteria
Identify and grade treatment-emergent laboratory abnormalities of escalating doses of BP1002 by identification and grading of [30 days]
Identify and grade treatment-emergent laboratory abnormalities of BP1002 using non-hematologic and hematologic measures per NCI CTCAE criteria
Identify conduction and rhythm changes (treatment emergent QTc elevations or other treatment emergent changes in EKG intervals) of escalating doses of BP1002 [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)
Recommended Phase 2 dose (RP2D) of BP1002 [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.
Determine plasma pharmacokinetics (PK) of BP1002 using maximum plasma drug concentration [30 days]
Evaluate in vivo PK of BP1002 using maximum plasma drug concentration (Cmax)
Determine plasma pharmacokinetics (PK) of BP1002 using volume of distribution [30 days]
Evaluate in vivo PK of BP1002 volume of distribution (Vd)
Determine plasma pharmacokinetics (PK) of BP1002 using elimination rate constant [30 days]
Evaluate in vivo PK of BP1002 elimination rate constant
Determine half-life plasma pharmacokinetics (PK) of BP1002 [30 days]
Evaluate in vivo PK of BP1002 half-life (t1/2)
Determine pharmacokinetics (PK) of BP1002 [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

Determine evidence of tumor response by bone marrow aspirate [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)
Determine evidence of tumor response by Complete Blood Count (CBC) [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)
Determine estimates for time to progression (TTP) [30 days]
Measured from treatment start date to date of progression by CBC and/or bone marrow aspirate
Determine estimates for progression-free survival (PFS) [30 days]
Measured from treatment start date to date of progression or death by CBC and/or bone marrow aspirate
Determine estimates for event-free survival (EFS) [30 days]
Measured from treatment start date to date of progression, death, or change in therapy by CBC and/or bone marrow aspirate
Activity of BP1002 on Bcl-2 expression in tumor samples [30 days]
Flow cytometric assays to determine the effects of BP1002 on Bcl-2 protein expression using patient blood samples

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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
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
Females must be of non-childbearing potential, surgically sterile, postmenopausal, or practice adequate methods of contraception during the study
Males must agree to use an adequate method of contraception during the study
Eastern Cooperative Oncology Group (ECOG) Performance score of 0, 1, or 2
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

Recovered from the effects of any prior surgery, radiotherapy, or antineoplastic treatment (with the exception of alopecia), based on Investigator assessment
Willing and able to provide written informed consent

Exclusion Criteria:

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)

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
Unable or unwilling to communicate or cooperate with the Investigator or follow the protocol for any reason.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Georgia Cancer Center	Augusta	Georgia	United States	30912
2	Sarah Cannon Research Institute/Tennesee Oncology	Nashville	Tennessee	United States	37203
3	MD Anderson Cancer Research Center	Houston	Texas	United States	77030