A Clinical Trial of BP1002 in Patients With Advanced Lymphoid Malignancies

Bio-Path

Status and phase: Active, not recruiting; Phase 1

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

Treatments: Drug: L-Bcl-2 antisense oligonucleotide

Study type: Interventional

Funder types: Industry

Identifiers

NCT04072458

BP1002-101-Lymph

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

BP1002 monotherapy

Experimental group

Description:

L-Bcl-2 Antisense oligonucleotide (BP1002) is given in a sequential, dose escalation design. Starting dose is 20mg/m\^2.

Treatment:

Drug: L-Bcl-2 antisense oligonucleotide