Phase 1/2a Trial of BI-1206, a Monoclonal Antibody to CD32b (FcyRIIB), in Combination With Rituximab With or Without Acalabrutinib in Subjects With Indolent B-Cell Non-Hodgkin Lymphoma That Has Relapsed or is Refractory to Rituximab
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 27
- 主要终点
- Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or rituximab and/or acalabrutinib
研究概览
简要总结
Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcyRIIB), in Combination with Rituximab with or without Acalabrutinib in Subjects with Indolent B-Cell Non-Hodgkin Lymphoma That has Relapsed or is Refractory to Rituximab
详细描述
This is a Phase 1/2a, multicenter, dose escalation, consecutive-cohort, open-label trial of BI-1206 in combination with rituximab with or without acalabrutinib in subjects with indolent relapsed or refractory B-cell NHL, sub-types FL (except FL grade 3B), MZL, and MCL.
Phase 2a, consists of signal seeking cohorts followed by a randomized, parallel, two-arm dose optimization.
The trial consists of 2 main parts:
Phase 1
- Dose Escalation, with two different Arms assessing IV or SC dosing of BI-1206 in combination with rituximab, with dose escalation cohorts and selection of the IV and SC doses of BI-1206 for Phase 2a
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Are ≥ 18 years of age by initiation of study treatment.
- •Have B-cell NHL proven by histology, with histological subtypes limited to follicular lymphoma (FL) (except FL grade 3B), MCL and marginal zone lymphoma (MZL)
- •Have measurable nodal disease
- •Are willing to undergo lymph node biopsies or biopsies of other involved tissue
- •Have relapsed disease or disease refractory to conventional treatment or for which no standard therapy exists
- •Have received at least one line of conventional previous therapy which must include at least one rituximab-based regimen
- •Have a life expectancy of at least 12 weeks
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Have CD20+ malignancy
- •Have hematological and biochemical indices within prespecified ranges
排除标准
- •Have had an allogenic bone marrow or stem cell transplant within 12 months
- •Have presence of active chronic graft versus host disease
- •Have current leptomeningeal lymphoma or compromise of the central nervous system
- •Have transformed lymphoma from a pre-existing indolent lymphoma
- •Have Waldenstrom's Macroglobulinemia or FL grade 3B,
- •Need systemic doses of prednisolone >10 mg daily (or equipotent doses of other corticosteroids) while on the study trial other than as pre-medication.
- •Have known or suspected hypersensitivity to rituximab or BI-1206
- •Have cardiac or renal amyloid light-chain amyloidosis
- •Have received any of the following:
- •Chemotherapy or small molecule products with 2 weeks of first dose of BI-1206
- •Radiotherapy (except for focal symptomatic control of lymphadenopathy) within 4 weeks
- •Immunotherapy within 8 weeks
- •Previous lines of treatment containing BTK inhibitors for Subjects receiving BI-1206 in combination with rituximab and acalabrutinib
- •Have ongoing toxic manifestations of previous treatments.
- •Have the ability to become pregnant (or already pregnant or lactating/breastfeeding).
- •Have had major surgery from which the subject has not yet recovered.
- •Are at high medical risk because of non-malignant systemic disease including active infection on treatment with antibiotics, antifungals or antivirals.
- •Are serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
- •Have an active, known or suspected autoimmune disease.
- •Have concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA])
- •Have current malignancies of other types
研究组 & 干预措施
BI-1206 IV Dose Escalation
Standard 3+3 Dose-Escalation of BI-1206 IV in combination with Rituximab
干预措施: BI-1206 (Biological)
BI-1206 IV Dose Escalation
Standard 3+3 Dose-Escalation of BI-1206 IV in combination with Rituximab
干预措施: Rituximab (Biological)
BI-1206 SC Dose Escalation
Adaptive Dose Escalation of BI-1206 SC (Bayesian logistic regression model (BLRM) in combination with Rituximab
干预措施: BI-1206 (Biological)
BI-1206 SC Dose Escalation
Adaptive Dose Escalation of BI-1206 SC (Bayesian logistic regression model (BLRM) in combination with Rituximab
干预措施: Rituximab (Biological)
Phase 2a IV Dose expansion
BI-1206 IV in Combination with Rituximab
干预措施: BI-1206 (Biological)
Phase 2a IV Dose expansion
BI-1206 IV in Combination with Rituximab
干预措施: Rituximab (Biological)
Phase 2a SC Signal seeking
SC Arm, BI-1206 in Combination with Rituximab and Acalabrutinib
干预措施: BI-1206 (Biological)
Phase 2a SC Signal seeking
SC Arm, BI-1206 in Combination with Rituximab and Acalabrutinib
干预措施: Rituximab (Biological)
Phase 2a SC Signal seeking
SC Arm, BI-1206 in Combination with Rituximab and Acalabrutinib
干预措施: Acalabrutinib (Biological)
Phase 2a IV Signal Seeking
IV Arm, BI-1206 in Combination with Rituximab and Acalabrutinib
干预措施: BI-1206 (Biological)
Phase 2a IV Signal Seeking
IV Arm, BI-1206 in Combination with Rituximab and Acalabrutinib
干预措施: Rituximab (Biological)
Phase 2a IV Signal Seeking
IV Arm, BI-1206 in Combination with Rituximab and Acalabrutinib
干预措施: Acalabrutinib (Biological)
结局指标
主要结局
Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or rituximab and/or acalabrutinib
时间窗: During the 28-day treatment period on induction therapy
Assess the safety and tolerability profile of BI-1206 when administered intravenously (IV) or subcutaneously (SC) in combination with rituximab or rituximab and acalabrutinib in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL), subtypes follicular lymphoma (FL)(except FL grade 3B), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL). Assessment will be done according to National Cancer Institute (NCI-CTCAE) criteria v. 5.0.
Determining the MTD of BI-1206 at the same dose level experiencing a BI-1206 or Rituximab-related or possibly related dose-limiting toxicity (DLT)
时间窗: During the 28-day treatment period on induction therapy
Phase 1: Select the recommended Phase 2 dose (RP2D) by establishing the maximum tolerated dose (MTD) of BI-1206 given once weekly for 4 weeks, via IV infusion or SC injection in combination with rituximab.
Determine the recommended dose of BI-1206 in combination with rituximab and acalabrutinib
时间窗: During the 28-day treatment period on induction therapy
Phase 2a: Select the recommended dose of BI-1206 in combination with rituximab and acalabrutinib.
次要结局
- Evaluation of PK parameters for BI-1206(Up to 1 year)
- Evaluation of ADA (immunogenicity) response to BI-1206(Up to 1 year)
- Measurement of peripheral blood B-lymphocytes depletion(Up to 1 year)
- Assessment of overall response rate (ORR) according to the response criteria for malignant lymphoma (Cheson, 2014).(Up to 1 year)