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

Официальное название

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

Обзор

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

Подробное описание

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

Вмешательства

• Биопрепарат BI-1206
  BI-1206 150 mg / 225 mg Subcutaneous injection BI-1206 50 mg /100 mg Intravenous infusion
• Биопрепарат Rituximab
  Rituximab 375 mg/m2, as per SmPC
• Биопрепарат Acalabrutinib
  Acalabrutinib 100 mg orally as per SmPC

Первичные конечные точки

• Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or rituximab and/or acalabrutinib [Срок оценки: 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) [Срок оценки: During the 28-day treatment period on induction therapy]
• Determine the recommended dose of BI-1206 in combination with rituximab and acalabrutinib [Срок оценки: During the 28-day treatment period on induction therapy]

Вторичные конечные точки (4)

• Evaluation of PK parameters for BI-1206 [Срок оценки: Up to 1 year]
• Evaluation of ADA (immunogenicity) response to BI-1206 [Срок оценки: Up to 1 year]
• Measurement of peripheral blood B-lymphocytes depletion [Срок оценки: Up to 1 year]
• Assessment of overall response rate (ORR) according to the response criteria for malignant lymphoma (Cheson, 2014). [Срок оценки: Up to 1 year]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Бразилия · 10 центров

• Hospital São Rafael — Salvador
• Hospital de Clínicas de Porto Alegre — Porto Alegre
• Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer — Curitiba
• Ruschel Medicina e Pesquisa Clínica — Rio de Janeiro
• A.C. Camargo Cancer Center — São Paulo
• Hospital Amaral Carvalho — São Paulo
• Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo — São Paulo
• Hospital Israelita Albert Einstein — São Paulo
• … и ещё 2 центра

Испания · 9 центров

• Hospital ICO, Trias i Pujol — Badalona
• Hospital de la Santa Creu i Sant Pau, Dep Hematologia — Barcelona
• Hospital Universitari Vall d'Hebron — Barcelona
• Institut Català d'Oncologia, L'Hospitalet de Llobregat — Barcelona
• Hospital General Universitario Gregorio Marañon-Oncología Médica — Madrid
• Hospital Universitario HM Sanchinarro — Madrid
• University Hospital Fundacion Jimenez Diaz — Madrid
• Hospital Universitario Virgen de la Arrixaca — Murcia
• … и ещё 1 центр

США · 2 центра

• Emory University Hospital — Atlanta
• Norton Cancer Institute - St. Matthews 3991 Dutchmans Lane Medical Plaza II, Suite 405 — Louisville

Германия · 2 центра

• Krankenhaus Nordwest Klinik für Onkologie und Hämatologie — Frankfurt am Main
• Robert Bosch Hospital, Dep of Hematology, Oncology and Palliative care — Stuttgart

Польша · 2 центра

• Szpital Specjlistyczny — Grudziądz
• Małopolskie Centrum Medyczne — Krakow

Швеция · 2 центра

• Department of Oncology, Skåne University Hospital — Lund
• Department of Oncology, Academical Hospital — Uppsala

Идентификаторы

NCT: NCT03571568 · 17-BI-1206-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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