A Study of BI-1206 in Combination With Rituximab in Subjects With Indolent B-Cell Non-Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcyRIIB), in Combination with Rituximab in Subjects with Indolent B-Cell Non-Hodgkin Lymphoma That has Relapsed or is Refractory to Rituximab
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
This is a Phase 1/2a, dose escalation, consecutive-cohort, open-label studytrial of BI-1206 in combination with rituximab in subjects with indolent relapsed or refractory B-cell NHL. The studytrial will consist of 2 main parts: Phase 1 (with dose escalation cohorts using a 3+3 dose-escalation design and selection of the RP2D), and Phase 2a (the escalationexpansion cohort at the RP2D). Subjects in each phase will receive 1 cycle (4 doses) of induction therapy with BI-1206 in combination with rituximab. Subjects who show clinical benefit (complete response [CR], partial response [PR], or stable disease [SD]) at Week 6 will continue onto maintenance therapy and receive BI-1206 and rituximab once every 8 weeks (relative to previous maintenance dose) for up to 6 maintenance cycles, or up to 1 year from first dose of BI-1206 (whichever occurs first).
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: BI-1206 BI-1206 IV Standard 3+3 Dose-Escalation Design |
Biological: BI1206
375 mg/m2, as per SmPC
Other Names:
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Outcome Measures
Primary Outcome Measures
- Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or rituximab [During the 28-day treatment period on induction therapy]
Assess the safety and tolerability profile of BI-1206 when administered in combination with Rituximab
- 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]
Select the RP2D
Secondary Outcome Measures
- Evaluation of PK parameters for BI-1206. Maximum observed plasma concentration (Cmax) [Up to 1 year]
Study the PK profile of BI-1206 together with Rituximab
- Evaluation of PK parameters for BI-1206. Area under the plasma concentration-time curve (AUC) [Up to 1 year]
Study the PK profile of BI-1206 together with Rituximab
- Evaluation of PK parameters for Rituximab. Maximum observed plasma concentration (Cmax) [Up to 1 year]
Study the PK profile of Rituximab together with BI-1206
- Evaluation of PK parameters for Rituximab. Area under the plasma concentration-time curve (AUC) [Up to 1 year]
Study the PK profile of Rituximab together with BI-1206
- Evaluation of ADA response to BI 1206 [Up to 1 year]
Assess the immunogenicity of BI-1206
- Measurement of B cell depletion [Up to 1 year]
Evaluate the effect of BI-1206
- Assessment of overall response rate (response criteria for malignant lymphoma (Cheson, 2014). RR) [Up to 1 year]
Assess possible anti-tumor activity of BI-1206
Eligibility Criteria
Criteria
Inclusion Criteria:
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Are ≥ 18 years of age by initiation of study treatment.
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Have B-cell NHL proven by histology, with histological subtypes limited to follicular lymphoma (FL) (except FL3B), MCL and marginal zone lymphoma (MZL).
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Have measureable nodal disease
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Are willing to undergo lymph node biopsies or biopsies of other involved tissue
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Have relapsed disease or disease refractory to conventional treatment or for which no standard therapy exists.
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Have received at least one line of conventional previous therapy which must include at least one rituximab-based regimen.
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Have a life expectancy of at least 12 weeks
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Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
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Have CD20+ malignancy
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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 FL3B,
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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 the following:
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Chemotherapy or small molecule products with 2 weeks of first dose of BI-1206
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Radiotherapy (except for focal symptomatic control of lymphadenopathy) within 4 weeks
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Immunotherapy within 8 weeks
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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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Emory University Hospital | Atlanta | Georgia | United States | 30322 |
2 | Szpital Specjlistyczny | Grudziadz | Poland | 86-300 | |
3 | Małopolskie Centrum Medyczne | Krakow | Poland | ||
4 | Hospital ICO, Trias i Pujol | Badalona | Spain | ||
5 | Hospital Duran i Reynals Av. | Barcelona | Spain | ||
6 | Hospital Universitari Vall d'Hebron | Barcelona | Spain | ||
7 | University Hospital Fundacion Jimenez Diaz | Madrid | Spain | ||
8 | Department of Oncology, Skåne University Hospital | Lund | Sweden | SE-22185 | |
9 | Department of Oncology, Academical Hospital | Uppsala | Sweden | 751 85 |
Sponsors and Collaborators
- BioInvent International AB
Investigators
- Principal Investigator: Mats Jerkeman, MD PhD, Senior Consultant and Adjunct Professor, Skane Univ Hospital, Lund, Sweden
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 17-BI-1206-02