Clinical trial NCT04072458: A Clinical Trial of BP1002 in Patients With Advanced Lymphoid Malignancies
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
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
Lead sponsor: Bio-Path Holdings, Inc.
Sponsor class: INDUSTRY
First posted: 2019-08-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Identify Dose Limiting Toxicity (DLT) of BP1002
timeFrame: 30 days
measure: Identify and grade treatment-emergent adverse events (TEAE) of escalating doses of BP1002
timeFrame: 30 days
measure: Identify and grade treatment-emergent laboratory abnormalities of escalating doses of BP1002 by identification and grading of
timeFrame: 30 days
measure: Identify conduction and rhythm changes (treatment emergent QTc elevations or other treatment emergent changes in EKG intervals) of escalating doses of BP1002
timeFrame: 30 days
measure: Recommended Phase 2 dose (RP2D) of BP1002
timeFrame: 210 days
measure: Determine plasma pharmacokinetics (PK) of BP1002 using maximum plasma drug concentration
timeFrame: 30 days
measure: Determine plasma pharmacokinetics (PK) of BP1002 using volume of distribution
timeFrame: 30 days
measure: Determine plasma pharmacokinetics (PK) of BP1002 using elimination rate constant
timeFrame: 30 days
measure: Determine half-life plasma pharmacokinetics (PK) of BP1002
timeFrame: 30 days
measure: Determine pharmacokinetics (PK) of BP1002
timeFrame: 30 days
Secondary outcomes:
measure: Determine evidence of tumor response by bone marrow aspirate
timeFrame: 30 days
measure: Determine evidence of tumor response by Complete Blood Count (CBC)
timeFrame: 30 days
measure: Determine estimates for time to progression (TTP)
timeFrame: 30 days
measure: Determine estimates for progression-free survival (PFS)
timeFrame: 30 days
measure: Determine estimates for event-free survival (EFS)
timeFrame: 30 days
measure: Activity of BP1002 on Bcl-2 expression in tumor samples
timeFrame: 30 days
Other outcomes:
measure: Exploratory objective to correlate treatment response with cytogenetic characteristics
timeFrame: 30 days
measure: Exploratory objective to correlate treatment response with molecular characteristics
timeFrame: 30 days
Locations:
city: Augusta
country: United States
facility: Georgia Cancer Center
state: Georgia
city: Valhalla
country: United States
facility: New York Medical College / Westchester Medical Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute/Tennesee Oncology
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Research Center
state: Texas
Study officials:
References: