Um estudo de BI-1206 em combinação com rituximabe em indivíduos com linfoma não Hodgkin indolente de células B
Ensaio clínico de fase 1/2a de BI-1206, um anticorpo monoclonal para CD32b (FcYRIIB), em combinação com rituximabe em indivíduos com linfoma não Hodgkin indolente de células B que recidivou ou é refratário ao rituximabe
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
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
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
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
- Fase 1
Contactos e Locais
Contato de estudo
- Nome: Erika Bågeman
- Número de telefone: +46706126618
- E-mail: erika.bageman@bioinvent.com
Estude backup de contato
- Nome: Andres McAllister, MD, PhD
- E-mail: andres.mcallister@bioinvent.com
Locais de estudo
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Stuttgart, Alemanha
- Retirado
- Robert Bosch Hospital, Dep of Hematology, Oncology and Palliative care
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Hesse
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Frankfurt am Main, Hesse, Alemanha
- Ainda não está recrutando
- Krankenhaus Nordwest Klinik für Onkologie und Hämatologie
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Investigador principal:
- Eckhart Weidmann, MD
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Contato:
- E-mail: weidmann.eckhart@khnw.de
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Curitiba, Brasil
- Ainda não está recrutando
- Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
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Contato:
- E-mail: munhoz.ec@gmail.com
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Investigador principal:
- Eduardo Munhoz, MD
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Rio de Janeiro, Brasil
- Ainda não está recrutando
- Ruschel Medicina e Pesquisa Clínica
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Contato:
- Thaiane Alexandre, RN
- E-mail: thaianealexandre@ruschelmedicina.com.br
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Investigador principal:
- Rony Schaffel, MD
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São Paulo, Brasil
- Ainda não está recrutando
- Hospital Samaritano
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Contato:
- E-mail: carlos.chiattone@terra.com.br
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Investigador principal:
- Carlos Chiattone, MD
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São Paulo, Brasil
- Ainda não está recrutando
- Hospital Sírio-Libanês
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Investigador principal:
- Ana Rita Da Fonseca, MD
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Contato:
- E-mail: anaritafonsecabm@gmail.com
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São Paulo, Brasil
- Ainda não está recrutando
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
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Contato:
- Camila Hinsching, RN
- E-mail: camila.f@hc.fm.usp.br
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Investigador principal:
- Juliana Pereira, MD
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São Paulo, Brasil
- Recrutamento
- A.C. Camargo Cancer Center
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Investigador principal:
- Ana Costa Cordeiro, MD
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Contato:
- E-mail: ana.cordeiro@accamargo.org.br
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São Paulo, Brasil
- Ainda não está recrutando
- Hospital Amaral Carvalho
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Contato:
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Investigador principal:
- Ederson Roberto De Mattos, MD
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São Paulo, Brasil
- Recrutamento
- Hospital Israelita Albert Einstein
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Investigador principal:
- Guilherme Perini, MD
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Contato:
- E-mail: guiperini@gmail.com
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Estado de Bahia
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Salvador, Estado de Bahia, Brasil
- Recrutamento
- Hospital São Rafael
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Contato:
- Cacilda
- E-mail: analuziaschriefer@gmail.com
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Investigador principal:
- Ana Luiza Schriefer, MD
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Rio Grande do Sul
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Porto Alegre, Rio Grande do Sul, Brasil
- Recrutamento
- Hospital de Clínicas de Porto Alegre
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Investigador principal:
- Laura Maria Fogliatto, MD
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Contato:
- Suellen
- E-mail: fogliattopesquisa@gmail.com
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Barcelona, Espanha
- Recrutamento
- Institut Català d'Oncologia, L'Hospitalet de Llobregat
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Investigador principal:
- Eva Domingo Domenech, MD
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Contato:
- E-mail: edomingo@iconcologia.net
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Madrid, Espanha
- Recrutamento
- University Hospital Fundacion Jimenez Diaz
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Investigador principal:
- Raul Cordoba Mascunano, MD
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Contato:
- E-mail: raul.cordoba@fjd.es
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Barcelona
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Badalona, Barcelona, Espanha
- Recrutamento
- Hospital ICO, Trias i Pujol
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Investigador principal:
- Juan Manuel Sancho Cia, MA
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Contato:
- E-mail: jsancho@iconcologia.net
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Barcelona, Barcelona, Espanha
- Recrutamento
- Hospital Universitari Vall d'Hebron
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Investigador principal:
- Pablo Abrisqueta Costa, MD
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Contato:
- E-mail: pabrisqueta@vhio.net
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Barcelona, Barcelona, Espanha
- Recrutamento
- Hospital de la Santa Creu i Sant Pau, Dep Hematologia
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Contato:
- E-mail: smiqueleiz@santpau.cat
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Investigador principal:
- Sara Miqueleiz Alamos, MD
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Madrid
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Madrid, Madrid, Espanha
- Recrutamento
- Hospital Universitario HM Sanchinarro
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Contato:
- Agustín Penedo Coello
- E-mail: apenedo@hmhospitales.com
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Investigador principal:
- Augustin Penedo Coello, MD
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Madrid, Madrid, Espanha
- Recrutamento
- Hospital General Universitario Gregorio Marañon-Oncología Médica
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Investigador principal:
- Mariana Bastos Oreiro, MD
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Contato:
- E-mail: bastosmariana@yahoo.com
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Murcia
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Murcia, Murcia, Espanha
- Ainda não está recrutando
- Hospital Universitario Virgen de la Arrixaca
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Investigador principal:
- Joaquin Gomez Espuch, MD
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Contato:
- E-mail: joaquingomezespuch@hotmail.com
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Seville
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Seville, Seville, Espanha
- Recrutamento
- Hospital University Virgen Macarene
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Investigador principal:
- Sergio Ortegon Alcaide, MD
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Contato:
- Sergio Ortegón Alcaide
- E-mail: sortegonalcaide@gmail.com
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Ativo, não recrutando
- Emory University Hospital
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Kentucky
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Louisville, Kentucky, Estados Unidos, 40207
- Recrutamento
- Norton Cancer Institute - St. Matthews 3991 Dutchmans Lane Medical Plaza II, Suite 405
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Investigador principal:
- Don Stevens, MD
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Grudziądz, Polônia, 86-300
- Rescindido
- Szpital Specjlistyczny
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Krakow, Polônia
- Rescindido
- Małopolskie Centrum Medyczne
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Lund, Suécia, SE-22185
- Rescindido
- Department of Oncology, Skåne University Hospital
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Sweden
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Uppsala, Sweden, Suécia, 751 85
- Rescindido
- Department of Oncology, Academical Hospital
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- 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
Exclusion Criteria:
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Have had an allogenic bone marrow or stem cell transplant within 12 months
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Have presence of active chronic graft versus host disease
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Have current leptomeningeal lymphoma or compromise of the central nervous system
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Have transformed lymphoma from a pre-existing indolent lymphoma
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Have Waldenstrom's Macroglobulinemia or FL grade 3B,
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Need systemic doses of prednisolone >10 mg daily (or equipotent doses of other corticosteroids) while on the study trial other than as pre-medication.
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Have known or suspected hypersensitivity to rituximab or BI-1206
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Have cardiac or renal amyloid light-chain amyloidosis
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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
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Have ongoing toxic manifestations of previous treatments.
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Have the ability to become pregnant (or already pregnant or lactating/breastfeeding).
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Have had major surgery from which the subject has not yet recovered.
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Are at high medical risk because of non-malignant systemic disease including active infection on treatment with antibiotics, antifungals or antivirals.
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Are serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
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Have an active, known or suspected autoimmune disease.
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Have concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA])
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Have current malignancies of other types
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: BI-1206 IV Dose Escalation
Standard 3+3 Dose-Escalation of BI-1206 IV in combination with Rituximab |
BI-1206 150 mg / 225 mg Subcutaneous injection BI-1206 50 mg /100 mg Intravenous infusion Rituximab 375 mg/m2, as per SmPC
Outros nomes:
|
|
Experimental: BI-1206 SC Dose Escalation
Adaptive Dose Escalation of BI-1206 SC (Bayesian logistic regression model (BLRM) in combination with Rituximab |
BI-1206 150 mg / 225 mg Subcutaneous injection BI-1206 50 mg /100 mg Intravenous infusion Rituximab 375 mg/m2, as per SmPC
Outros nomes:
|
|
Experimental: Phase 2a IV Dose expansion
BI-1206 IV in Combination with Rituximab |
BI-1206 150 mg / 225 mg Subcutaneous injection BI-1206 50 mg /100 mg Intravenous infusion Rituximab 375 mg/m2, as per SmPC
Outros nomes:
|
|
Experimental: Phase 2a SC Signal seeking
SC Arm, BI-1206 in Combination with Rituximab and Acalabrutinib |
BI-1206 150 mg / 225 mg Subcutaneous injection BI-1206 50 mg /100 mg Intravenous infusion Rituximab 375 mg/m2, as per SmPC
Outros nomes:
Acalabrutinib 100 mg orally as per SmPC
Outros nomes:
|
|
Experimental: Phase 2a IV Signal Seeking
IV Arm, BI-1206 in Combination with Rituximab and Acalabrutinib |
BI-1206 150 mg / 225 mg Subcutaneous injection BI-1206 50 mg /100 mg Intravenous infusion Rituximab 375 mg/m2, as per SmPC
Outros nomes:
Acalabrutinib 100 mg orally as per SmPC
Outros nomes:
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or rituximab and/or acalabrutinib
Prazo: 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. |
During the 28-day treatment period on induction therapy
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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)
Prazo: 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. |
During the 28-day treatment period on induction therapy
|
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Determine the recommended dose of BI-1206 in combination with rituximab and acalabrutinib
Prazo: During the 28-day treatment period on induction therapy
|
Phase 2a: Select the recommended dose of BI-1206 in combination with rituximab and acalabrutinib. |
During the 28-day treatment period on induction therapy
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Evaluation of PK parameters for BI-1206
Prazo: 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 |
Up to 1 year
|
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Evaluation of ADA (immunogenicity) response to BI-1206
Prazo: 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. |
Up to 1 year
|
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Measurement of peripheral blood B-lymphocytes depletion
Prazo: 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. |
Up to 1 year
|
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Assessment of overall response rate (ORR) according to the response criteria for malignant lymphoma (Cheson, 2014).
Prazo: 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. |
Up to 1 year
|
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Expression levels of CD32b protein
Prazo: Up to 1 year
|
To investigate CD32b protein expression levels using flow cytometry to evaluate any potential correlation with clinical responses. Change from baseline expression levels will be summarized descriptively by dose cohort and/or response to treatment. |
Up to 1 year
|
|
Assessment of Patient Reported Outcomes using the NCI PRO-CTCAE questionnaire
Prazo: Up to 1 year
|
The NCI PRO-CTCAE will be used to evaluate symptomatic toxicities reported by patients. The questionnaire characterizes the frequency, severity, interference, and presence/absence of symptomatic toxicities, all toxicities that can be meaningfully reported from the patient perspective. Responses are scored from 0 to 4 (or 0/1 for absent/present). Scores for each attribute (frequency, severity and/or interference) will be presented descriptively (e.g. summary statistics or graphical presentations). |
Up to 1 year
|
|
Expression levels of CD32b and/or other immunological markers
Prazo: Up to 1 year
|
Perform whole-transcriptome, quantitative polymerase chain reaction (qPCR) and/or IHC analysis of lymph node biopsies to evaluate potential correlation with clinical responses. |
Up to 1 year
|
|
Measurement of serum cytokines levels and/or soluble CD32b.
Prazo: Up to 1 year
|
Study the potential cause of infusion related reactions (IRRs), such as cytokine release signs, C-reactive protein (CRP) and/or soluble CD32b. |
Up to 1 year
|
Colaboradores e Investigadores
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 17-BI-1206-02
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
All information concerning the product as well as any matter concerning the operation of the Sponsor, such as clinical indications for the drug, its formula, methods of manufacture and other scientific data relating to it, that have been provided by the Sponsor and are unpublished, are confidential and must remain the sole property of the Sponsor. The Investigator will agree to use the information only for the purposes of carrying out this study and for no other purpose unless prior written permission from the Sponsor is obtained.
Prazo de Compartilhamento de IPD
Within one year from end of study
Critérios de acesso de compartilhamento IPD
Paper copy of CSR
Tipo de informação de suporte de compartilhamento de IPD
- PROTOCOLO DE ESTUDO
- CSR
Informações sobre medicamentos e dispositivos, documentos de estudo
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