Phase 1b Study of Teclistamab in Relapsed/Refractory Plasmablastic Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 6
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This phase Ib trial tests the safety, side effects, and best dose of teclistamab in treating patients with plasmablastic lymphoma that has come back after a period of improvement (recurrent) or that has not responded to previous treatment (refractory). Teclistamab is a bispecific antibody that can bind to two different antigens at the same time. Teclistamab binds to B-cell maturation antigen (BCMA), a protein found on some B-cells and myeloma cells, and CD3 on T-cells (a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Giving teclistamab may be safe and tolerable in treating patients with recurrent or refractory plasmablastic lymphoma.
详细描述
PRIMARY OBJECTIVE:
I. To determine the recommended phase 2 dose (RP2D) of teclistamab in relapsed/refractory (R/R) plasmablastic lymphoma (PBL).
SECONDARY OBJECTIVES:
I. To estimate the overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS), and overall survival (OS) of teclistamab in R/R PBL.
II. To observe and record anti-tumor activity.
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
- •Patients must have histologically or cytologically confirmed R/R PBL
- •Patients must have measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as ≥ 1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as ≥ 1.0 cm in its longest dimension
- •Patients should have ≥ 1 line of prior therapy. This includes at least 1 prior line of chemotherapy or radiation
- •Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of teclistamab in patients < 18 years of age, children are excluded from this study
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
- •Hemoglobin ≥ 8 g/dL, transfusion permitted if ≥ 7 days
- •Absolute neutrophil count ≥ 1,000/mcL
- •Platelets ≥ 75,000/mcL
- •Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN)
- •Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x institutional ULN
- •Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m^2
- •Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- •For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- •Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- •Patients with central nervous system (CNS) lymphoma are eligible if they have no CNS-related symptoms at study entry, and the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
- •Patients should either have received an autologous transplant or not be a candidate for one
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- •Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
- •Based on the mechanism of action, teclistamab may cause fetal harm when administered to a pregnant woman. Females of child-bearing potential (FCBP) should use effective contraception during treatment with teclistamab and for 6 months after the last dose. FCBP should not breast feed during treatment with teclistamab and for 6 months after the last dose. Should a FCBP become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Male patients with a partner who is a FCBP should use effective contraception during treatment and for 3 months after the last dose of teclistamab. Women of childbearing age should not donate eggs and men should not donate sperm for the duration of study participation. Women should not donate eggs for 6 months and men should not donate sperm for 3 months after completion of the last dose of study drug
- •Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
- •Vaccination with live virus vaccines is not recommended for at least 4 weeks prior to the start of treatment, during treatment and at least 4 weeks after treatment
排除标准
- •Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia and peripheral neuropathy
- •Patients who are receiving any other investigational agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to teclistamab
- •Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
- •Pregnant women are excluded from this study because teclistamab is a bispecific T-cell antibody agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with teclistamab, breastfeeding should be discontinued if the mother is treated with teclistamab. These potential risks may also apply to other agents used in this study
- •Pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation
- •Corticosteroid use for purposes other than lymphoma symptom control
- •The use of inhaled corticosteroids is permitted
- •The use of mineralocorticoids for management of orthostatic hypotension is permitted
- •The use of physiologic doses of corticosteroids for management of adrenal insufficiency is permitted
- •Participants who require lymphoma symptom control during screening may receive steroids in the following manner:
- •Up to 100 mg/day of prednisone or equivalent may be used for lymphoma symptom control during screening
- •Prior treatment with B-cell maturation antigen (BCMA)-targeted therapies
- •Prior treatment with T-cell engager therapies (bispecific, CAR-T, etc.) within the last 6 months
研究组 & 干预措施
Treatment (teclistamab)
Patients receive teclistamab SC on days 1, 4, and 7 in the absence of disease progression or unacceptable toxicity (i.e., Cycle 1). Beginning 1 week later, patients receive teclistamab SC on day 1 (i.e., Cycle 2). Beginning 1 week later, 2 weeks later, or 4 weeks later (based on dose level), patients receive teclistamab SC on day 1 of remaining cycles. Based on dose level, cycles repeat weekly, every 2 weeks, or every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients who have achieved a CR by cycle 13 may discontinue study treatment. Patients achieving less than a CR but benefiting from treatment may continue to receive teclistamab beyond 13 cycles in the absence of disease progression, unacceptable toxicity, or achieving a CR. Additionally, patients undergo optional buccal swab collection at baseline and optional blood sample collection throughout the study. Patients also undergo PET/CT throughout the study.
干预措施: Computed Tomography (Procedure)
Treatment (teclistamab)
Patients receive teclistamab SC on days 1, 4, and 7 in the absence of disease progression or unacceptable toxicity (i.e., Cycle 1). Beginning 1 week later, patients receive teclistamab SC on day 1 (i.e., Cycle 2). Beginning 1 week later, 2 weeks later, or 4 weeks later (based on dose level), patients receive teclistamab SC on day 1 of remaining cycles. Based on dose level, cycles repeat weekly, every 2 weeks, or every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients who have achieved a CR by cycle 13 may discontinue study treatment. Patients achieving less than a CR but benefiting from treatment may continue to receive teclistamab beyond 13 cycles in the absence of disease progression, unacceptable toxicity, or achieving a CR. Additionally, patients undergo optional buccal swab collection at baseline and optional blood sample collection throughout the study. Patients also undergo PET/CT throughout the study.
干预措施: Biospecimen Collection (Procedure)
Treatment (teclistamab)
Patients receive teclistamab SC on days 1, 4, and 7 in the absence of disease progression or unacceptable toxicity (i.e., Cycle 1). Beginning 1 week later, patients receive teclistamab SC on day 1 (i.e., Cycle 2). Beginning 1 week later, 2 weeks later, or 4 weeks later (based on dose level), patients receive teclistamab SC on day 1 of remaining cycles. Based on dose level, cycles repeat weekly, every 2 weeks, or every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients who have achieved a CR by cycle 13 may discontinue study treatment. Patients achieving less than a CR but benefiting from treatment may continue to receive teclistamab beyond 13 cycles in the absence of disease progression, unacceptable toxicity, or achieving a CR. Additionally, patients undergo optional buccal swab collection at baseline and optional blood sample collection throughout the study. Patients also undergo PET/CT throughout the study.
干预措施: Positron Emission Tomography (Procedure)
Treatment (teclistamab)
Patients receive teclistamab SC on days 1, 4, and 7 in the absence of disease progression or unacceptable toxicity (i.e., Cycle 1). Beginning 1 week later, patients receive teclistamab SC on day 1 (i.e., Cycle 2). Beginning 1 week later, 2 weeks later, or 4 weeks later (based on dose level), patients receive teclistamab SC on day 1 of remaining cycles. Based on dose level, cycles repeat weekly, every 2 weeks, or every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients who have achieved a CR by cycle 13 may discontinue study treatment. Patients achieving less than a CR but benefiting from treatment may continue to receive teclistamab beyond 13 cycles in the absence of disease progression, unacceptable toxicity, or achieving a CR. Additionally, patients undergo optional buccal swab collection at baseline and optional blood sample collection throughout the study. Patients also undergo PET/CT throughout the study.
干预措施: Teclistamab (Drug)
结局指标
主要结局
Incidence of adverse events
时间窗: Up to 28 days after last dose of study treatment
Will be assessed by Common Terminology Criteria for Adverse Events version 5.0. and American Society for Transplantation and Cellular Therapy/Immune Effector Cell Associated Neurotoxicity Syndrome criteria/grading. Descriptive statistics will be employed in the analysis of all safety observations in this study.
次要结局
- Overall response rate (ORR)(Up to 2 years after last dose of study treatment)
- Overall survival (OS)(From start of protocol treatment to time of death due to any cause, assessed up to 2 years)
- Complete response rate(Up to 2 years after last dose of study treatment)
- Progression-free survival (PFS)(From start of protocol treatment to time of progressive disease/relapse or death due to any cause, whichever occurs earlier, assessed up to 2 years)