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NCT03571568PHASE1, PHASE2Recruiting

A Study of BI-1206 in Combination With Rituximab With or Without Acalabrutinib in Subjects With Indolent B-Cell NHL

BioInvent International AB

Start Date

5/16/2018

Completion Date

9/30/2026

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

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: 1. Are ≥ 18 years of age by initiation of study treatment. 2. 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) 3. Have measurable nodal disease 4. Are willing to undergo lymph node biopsies or biopsies of other involved tissue 5. Have relapsed disease or disease refractory to conventional treatment or for which no standard therapy exists 6. Have received at least one line of conventional previous therapy which must include at least one rituximab-based regimen 7. Have a life expectancy of at least 12 weeks 8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 9. Have CD20+ malignancy 10. Have hematological and biochemical indices within prespecified ranges Exclusion Criteria: 1. Have had an allogenic bone marrow or stem cell transplant within 12 months 2. Have presence of active chronic graft versus host disease 3. Have current leptomeningeal lymphoma or compromise of the central nervous system 4. Have transformed lymphoma from a pre-existing indolent lymphoma 5. Have Waldenstrom's Macroglobulinemia or FL grade 3B, 6. Need systemic doses of prednisolone \>10 mg daily (or equipotent doses of other corticosteroids) while on the study trial other than as pre-medication. 7. Have known or suspected hypersensitivity to rituximab or BI-1206 8. Have cardiac or renal amyloid light-chain amyloidosis 9. Have received any of the following: 1. Chemotherapy or small molecule products with 2 weeks of first dose of BI-1206 2. Radiotherapy (except for focal symptomatic control of lymphadenopathy) within 4 weeks 3. Immunotherapy within 8 weeks 4. Previous lines of treatment containing BTK inhibitors for Subjects receiving BI-1206 in combination with rituximab and acalabrutinib 10. Have ongoing toxic manifestations of previous treatments. 11. Have the ability to become pregnant (or already pregnant or lactating/breastfeeding). 12. Have had major surgery from which the subject has not yet recovered. 13. Are at high medical risk because of non-malignant systemic disease including active infection on treatment with antibiotics, antifungals or antivirals. 14. Are serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV). 15. Have an active, known or suspected autoimmune disease. 16. Have concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association \[NYHA\]) 17. Have current malignancies of other types

Interventions

BIOLOGICAL

BI-1206

BIOLOGICAL

Rituximab

BIOLOGICAL

Acalabrutinib

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Conditions

Indolent B-Cell Non-Hodgkin Lymphoma

Locations

Emory University Hospital

Atlanta, Georgia 30322

United States

Norton Cancer Institute - St. Matthews 3991 Dutchmans Lane Medical Plaza II, Suite 405

Louisville, Kentucky 40207

United States

Hospital São Rafael

Salvador, Estado de Bahia

Brazil

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul

Brazil

Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer

Curitiba,

Brazil

Ruschel Medicina e Pesquisa Clínica

Rio de Janeiro,

Brazil

A.C. Camargo Cancer Center

São Paulo,

Brazil

Hospital Amaral Carvalho

São Paulo,

Brazil

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo,

Brazil

Hospital Israelita Albert Einstein

São Paulo,

Brazil

Hospital Samaritano

São Paulo,

Brazil

Hospital Sírio-Libanês

São Paulo,

Brazil

Krankenhaus Nordwest Klinik für Onkologie und Hämatologie

Frankfurt am Main, Hesse

Germany

Robert Bosch Hospital, Dep of Hematology, Oncology and Palliative care

Stuttgart,

Germany

Szpital Specjlistyczny

Grudziądz, 86-300

Poland

Małopolskie Centrum Medyczne

Krakow,

Poland

Hospital ICO, Trias i Pujol

Badalona, Barcelona

Spain

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, SE-22185

Sweden

Department of Oncology, Academical Hospital

Uppsala, 751 85

Sweden