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
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 30
- 试验地点
- 5
- 主要终点
- Recommended Phase 2 dose (RP2D) of BP1002
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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)
- •a. 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.
研究组 & 干预措施
BP1002 monotherapy
L-Bcl-2 Antisense oligonucleotide (BP1002) is given in a sequential, dose escalation design. Starting dose is 20mg/m^2.
干预措施: L-Bcl-2 antisense oligonucleotide (Drug)
结局指标
主要结局
Recommended Phase 2 dose (RP2D) of BP1002
时间窗: 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
时间窗: 30 days
Evaluate in vivo PK of BP1002 using maximum plasma drug concentration (Cmax)
Determine plasma pharmacokinetics (PK) of BP1002 using volume of distribution
时间窗: 30 days
Evaluate in vivo PK of BP1002 volume of distribution (Vd)
Determine half-life plasma pharmacokinetics (PK) of BP1002
时间窗: 30 days
Evaluate in vivo PK of BP1002 half-life (t1/2)
Identify and grade treatment-emergent adverse events (TEAE) of escalating doses of BP1002
时间窗: 30 days
Identify TEAE of BP1002 using non-hematologic and hematologic measures per NCI CTCAE criteria
Identify Dose Limiting Toxicity (DLT) of BP1002
时间窗: 30 days
Identify DLT 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
时间窗: 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
时间窗: 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)
Determine plasma pharmacokinetics (PK) of BP1002 using elimination rate constant
时间窗: 30 days
Evaluate in vivo PK of BP1002 elimination rate constant
Determine pharmacokinetics (PK) of BP1002
时间窗: 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
次要结局
- Determine estimates for time to progression (TTP)(30 days)
- Activity of BP1002 on Bcl-2 expression in tumor samples(30 days)
- Determine evidence of tumor response by Complete Blood Count (CBC)(30 days)
- Determine evidence of tumor response by bone marrow aspirate(30 days)
- Determine estimates for progression-free survival (PFS)(30 days)
- Determine estimates for event-free survival (EFS)(30 days)