Clinical trial NCT03571568: A Study of BI-1206 in Combination With Rituximab With or Without Acalabrutinib in Subjects With Indolent B-Cell NHL
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Indolent B-Cell Non-Hodgkin Lymphoma
Lead sponsor: BioInvent International AB
Sponsor class: INDUSTRY
First posted: 2018-06-27
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Phase 1/2a, dose escalation, consecutive-cohort, open-label study trial of BI-1206 in combination with rituximab with or without Acalabrutinib
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or rituximab and/or acalabrutinib
timeFrame: During the 28-day treatment period on induction therapy
measure: 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)
timeFrame: During the 28-day treatment period on induction therapy
measure: Determine the recommended dose of BI-1206 in combination with rituximab and acalabrutinib
timeFrame: During the 28-day treatment period on induction therapy
Secondary outcomes:
measure: Evaluation of PK parameters for BI-1206
timeFrame: Up to 1 year
measure: Evaluation of ADA (immunogenicity) response to BI-1206
timeFrame: Up to 1 year
measure: Measurement of peripheral blood B-lymphocytes depletion
timeFrame: Up to 1 year
measure: Assessment of overall response rate (ORR) according to the response criteria for malignant lymphoma (Cheson, 2014).
timeFrame: Up to 1 year
Other outcomes:
measure: Expression levels of CD32b protein
timeFrame: Up to 1 year
measure: Assessment of Patient Reported Outcomes using the NCI PRO-CTCAE questionnaire
timeFrame: Up to 1 year
measure: Expression levels of CD32b and/or other immunological markers
timeFrame: Up to 1 year
measure: Measurement of serum cytokines levels and/or soluble CD32b.
timeFrame: Up to 1 year
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Louisville
country: United States
facility: Norton Cancer Institute - St. Matthews 3991 Dutchmans Lane Medical Plaza II, Suite 405
state: Kentucky
city: Salvador
country: Brazil
facility: Hospital São Rafael
state: Bahia
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: Rio Grande Do Sul
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
city: Rio De Janeiro
country: Brazil
facility: Ruschel Medicina e Pesquisa Clínica
city: Sao Paulo
country: Brazil
facility: Hospital Amaral Carvalho
city: São Paulo
country: Brazil
facility: A.C. Camargo Cancer Center
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
city: São Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
city: São Paulo
country: Brazil
facility: Hospital Samaritano
city: São Paulo
country: Brazil
facility: Hospital Sírio-Libanês
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest Klinik für Onkologie und Hämatologie
state: Hessen
city: Stuttgart
country: Germany
facility: Robert Bosch Hospital, Dep of Hematology, Oncology and Palliative care
city: Grudziadz
country: Poland
facility: Szpital Specjlistyczny
city: Krakow
country: Poland
facility: Małopolskie Centrum Medyczne
city: Badalona
country: Spain
facility: Hospital ICO, Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau, Dep Hematologia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia, L'Hospitalet de Llobregat
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon-Oncología Médica
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Madrid
country: Spain
facility: University Hospital Fundacion Jimenez Diaz
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Seville
country: Spain
facility: Hospital University Virgen Macarene
city: Lund
country: Sweden
facility: Department of Oncology, Skåne University Hospital
city: Uppsala
country: Sweden
facility: Department of Oncology, Academical Hospital
Study officials:
References: