A Study of BI-1206 in Combination With Rituximab With or Without Acalabrutinib in Subjects With Indolent B-Cell NHL
- Conditions
- Indolent B-Cell Non-Hodgkin Lymphoma
- Interventions
- Registration Number
- NCT03571568
- Lead Sponsor
- BioInvent International AB
- Brief Summary
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
- Detailed Description
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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 140
- 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
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BI-1206 IV Dose Escalation BI-1206 Standard 3+3 Dose-Escalation of BI-1206 IV in combination with Rituximab BI-1206 IV Dose Escalation Rituximab Standard 3+3 Dose-Escalation of BI-1206 IV in combination with Rituximab BI-1206 SC Dose Escalation BI-1206 Adaptive Dose Escalation of BI-1206 SC (Bayesian logistic regression model (BLRM) in combination with Rituximab BI-1206 SC Dose Escalation Rituximab Adaptive Dose Escalation of BI-1206 SC (Bayesian logistic regression model (BLRM) in combination with Rituximab Phase 2a IV Dose expansion BI-1206 BI-1206 IV in Combination with Rituximab Phase 2a IV Dose expansion Rituximab BI-1206 IV in Combination with Rituximab Phase 2a SC Signal seeking BI-1206 SC Arm, BI-1206 in Combination with Rituximab and Acalabrutinib Phase 2a SC Signal seeking Rituximab SC Arm, BI-1206 in Combination with Rituximab and Acalabrutinib Phase 2a SC Signal seeking Acalabrutinib SC Arm, BI-1206 in Combination with Rituximab and Acalabrutinib Phase 2a IV Signal Seeking BI-1206 IV Arm, BI-1206 in Combination with Rituximab and Acalabrutinib Phase 2a IV Signal Seeking Rituximab IV Arm, BI-1206 in Combination with Rituximab and Acalabrutinib Phase 2a IV Signal Seeking Acalabrutinib IV Arm, BI-1206 in Combination with Rituximab and Acalabrutinib BI-1206 SC BI-1206 BI-1206 SC Adaptive Dose Escalation Design (Bayesian logistic regression model (BLRM) BI-1206 IV BI-1206 BI-1206 IV Standard 3+3 Dose-Escalation Design
- Primary Outcome Measures
Name Time Method Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or rituximab and/or acalabrutinib 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) 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 During the 28-day treatment period on induction therapy Phase 2a:
Select the recommended dose of BI-1206 in combination with rituximab and acalabrutinib.
- Secondary Outcome Measures
Name Time Method Evaluation of PK parameters for BI-1206 Up to 1 year PK parameters assessed will include AUC, Cmax, time to Cmax and t1/2 of BI-1206 when administered IV or SC
Evaluation of ADA (immunogenicity) response to BI-1206 Up to 1 year 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.
Measurement of peripheral blood B-lymphocytes depletion Up to 1 year 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.
Assessment of overall response rate (ORR) according to the response criteria for malignant lymphoma (Cheson, 2014). Up to 1 year 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.
Trial Locations
- Locations (27)
Szpital Specjlistyczny
🇵🇱Grudziadz, Poland
Małopolskie Centrum Medyczne
🇵🇱Krakow, Poland
Hospital ICO, Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
🇧🇷Curitiba, Brazil
Ruschel Medicina e Pesquisa Clínica
🇧🇷Rio De Janeiro, Brazil
Hospital Amaral Carvalho
🇧🇷Sao Paulo, Brazil
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
🇧🇷São Paulo, Brazil
Hospital Samaritano
🇧🇷São Paulo, Brazil
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
Norton Cancer Institute - St. Matthews 3991 Dutchmans Lane Medical Plaza II, Suite 405
🇺🇸Louisville, Kentucky, United States
Hospital São Rafael
🇧🇷Salvador, Bahia, Brazil
Hospital de Clínicas de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
A.C. Camargo Cancer Center
🇧🇷São Paulo, Brazil
Hospital Israelita Albert Einstein
🇧🇷São Paulo, Brazil
Hospital Sírio-Libanês
🇧🇷São Paulo, Brazil
Krankenhaus Nordwest Klinik für Onkologie und Hämatologie
🇩🇪Frankfurt, Hessen, Germany
Robert Bosch Hospital, Dep of Hematology, Oncology and Palliative care
🇩🇪Stuttgart, Germany
Hospital de la Santa Creu i Sant Pau, Dep Hematologia
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Institut Català d'Oncologia, L'Hospitalet de Llobregat
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon-Oncología Médica
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
University Hospital Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Hospital University Virgen Macarene
🇪🇸Seville, Spain
Department of Oncology, Skåne University Hospital
🇸🇪Lund, Sweden
Department of Oncology, Academical Hospital
🇸🇪Uppsala, Sweden