Indolent B-Cell Non-Hodgkin Lymphoma
Conditions
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
Interventions
BIOLOGICALBI-1206
BI-1206 150 mg / 225 mg Subcutaneous injection BI-1206 50 mg /100 mg Intravenous infusion
BIOLOGICALRituximab
Rituximab 375 mg/m2, as per SmPC
BIOLOGICALAcalabrutinib
Acalabrutinib 100 mg orally as per SmPC
Sponsors
BioInvent International AB
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or rituximab and/or acalabrutinib | 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. |
| Determine the recommended dose of BI-1206 in combination with rituximab and acalabrutinib | During the 28-day treatment period on induction therapy | Phase 2a: Select the recommended dose of BI-1206 in combination with rituximab and acalabrutinib. |
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of ADA (immunogenicity) response to BI-1206 | 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. |
| Evaluation of PK parameters for BI-1206 | 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 |
| Measurement of peripheral blood B-lymphocytes depletion | 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. |
| Assessment of overall response rate (ORR) according to the response criteria for malignant lymphoma (Cheson, 2014). | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Patient Reported Outcomes using the NCI PRO-CTCAE questionnaire | 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). |
| Measurement of serum cytokines levels and/or soluble CD32b. | 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. |
| Expression levels of CD32b protein | 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. |
| Expression levels of CD32b and/or other immunological markers | 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. |
Countries
Brazil, Germany, Poland, Spain, Sweden, United States
Contacts
Primary ContactErika Bågeman
Backup ContactAndres McAllister, MD, PhD
Outcome results
None listed