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
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 Phase 2a * Dose Expansion, with one expansion cohort evaluating the selected IV dose of BI-1206 in combination with rituximab * Signal Seeking, assessing IV and SC dosing of BI-1206 in combination with rituximab and acalabrutinib. The Signal Seeking will consist of a Safety Run-in and an Expansion * Dose Optimization to select the recommended dose of BI-1206 in combination with rituximab and acalabrutinib
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
140
BI-1206 150 mg / 225 mg Subcutaneous injection BI-1206 50 mg /100 mg Intravenous infusion
Rituximab 375 mg/m2, as per SmPC
Acalabrutinib 100 mg orally as per SmPC
Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or rituximab and/or acalabrutinib
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.
Time frame: During the 28-day treatment period on induction therapy
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)
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.
Time frame: During the 28-day treatment period on induction therapy
Determine the recommended dose of BI-1206 in combination with rituximab and acalabrutinib
Phase 2a: Select the recommended dose of BI-1206 in combination with rituximab and acalabrutinib.
Time frame: During the 28-day treatment period on induction therapy
Evaluation of PK parameters for BI-1206
PK parameters assessed will include AUC, Cmax, time to Cmax and t1/2 of BI-1206 when administered IV or SC
Time frame: Up to 1 year
Evaluation of ADA (immunogenicity) response to BI-1206
Assess the incidence and titre of antidrug antibodies of BI-1206 in serum when administered IV or SC in combination with rituximab or rituximab and acalabrutinib.
Time frame: Up to 1 year
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Emory University Hospital
Atlanta, Georgia, United States
ACTIVE_NOT_RECRUITINGNorton Cancer Institute - St. Matthews 3991 Dutchmans Lane Medical Plaza II, Suite 405
Louisville, Kentucky, United States
RECRUITINGHospital São Rafael
Salvador, Estado de Bahia, Brazil
RECRUITINGHospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil
RECRUITINGHospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
Curitiba, Brazil
NOT_YET_RECRUITINGRuschel Medicina e Pesquisa Clínica
Rio de Janeiro, Brazil
NOT_YET_RECRUITINGA.C. Camargo Cancer Center
São Paulo, Brazil
RECRUITINGHospital Amaral Carvalho
São Paulo, Brazil
NOT_YET_RECRUITINGHospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
São Paulo, Brazil
NOT_YET_RECRUITINGHospital Israelita Albert Einstein
São Paulo, Brazil
RECRUITING...and 17 more locations
Measurement of peripheral blood B-lymphocytes depletion
Evaluate the effect of BI-1206 administered IV or SC in combination with rituximab or rituximab and acalabrutinib measuring B Lymphocytes CD19+ (absolute value) as part of hematology assessment to determine the level of peripheral blood B lymphocyte depletion.
Time frame: Up to 1 year
Assessment of overall response rate (ORR) according to the response criteria for malignant lymphoma (Cheson, 2014).
Assess possible anti-tumor activity of BI-1206 administered IV or SC in combination with rituximab or rituximab and acalabrutinib at Week 6 after first dose of BI-1206 and for subjects who continue during maintenance therapy.
Time frame: Up to 1 year