Non-Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma
Conditions
Keywords
VAY736, ianalumab, lenalidomide, non-Hodgkin lymphoma, NHL, Diffuse large B cell lymphoma, DLBCL, Follicular lymphoma, FL, Mantle cell lymphoma, MCL, Marginal zone lymphoma, MZL
Brief summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK), immunogenicity and preliminary efficacy of VAY736 alone or in combination with other therapies in patients with NHL in a platform trial.
Detailed description
The primary objective of the study is to evaluate the safety and tolerability in patients with NHL and identify a maximum tolerated dose (MTD) and/or recommended dose (RD) of VAY736 single agent and in combination with other anti-cancer therapies. This is a phase I/Ib, multi-center, open-label study with multiple treatment arms in an adaptive study design. The study is comprised of a dose escalation part and dose expansion part. In dose escalation, the investigational drug VAY736 was explored alone or in combination with lenalidomide. Increasing doses of VAY736 alone or in combination were given to small groups of patients to identify the maximum tolerated dose/recommended dose (MTD/RD) in patients with NHL. In dose expansion, some or all the treatments from dose escalation could be tested at the recommended doses in patients with NHL. The study was expected to last approximately 4 years (from the enrollment of the first patient to the discontinuation of the last patient), but it was terminated early due to a business decision, not because of any safety or tolerability concerns. Consequently, the dose expansion part was not conducted.
Interventions
DRUGVAY736
VAY736 is a fully human IgG1 monoclonal antibody (mAb) which targets the B cell activating factor receptor (BAFF-R) expressed on the surface of differentiated B cells and modulates their function.
DRUGlenalidomide
Immune-modulatory agent that enhances activation of NK cells.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients with confirmed diagnosis of relapsed/refractory B-cell NHL with all subtypes of DLBCL, follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) per WHO 2016 criteria. Patients in subtype arm e.g. DLBCL must have confirmed diagnosis of relapsed/refractory DLBCL. * Received and failed or be intolerant to standard of care therapy (at least two prior lines, including an anti-CD20 therapy for NHL) * Must have measurable disease and ECOG of 0 to 2
Exclusion criteria
* Baseline laboratory results outside of protocol defined ranges * Patients with primary CNS lymphoma * History of hypersensitivity to VAY736 or any drugs in similar chemical classes (e.g. monoclonal antibodies) * Impaired cardiac function or clinically significant cardiac disease * History of or current interstitial lung disease or pneumonitis grade 2 or higher * HIV infection * Active hepatitis C infection and/or hepatitis B infection * Pregnant or nursing (lactating) women * Women of child-bearing potential unless they are using highly effective methods of contraception Other Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and nature of dose limiting toxicities (DLTs) | 28 days (first cycle of treatment) | Safety and tolerability |
| Incidence of Adverse events (AEs) and serious adverse events (SAEs) | 4 years | Incidence of AEs and SAEs is defined as number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs. |
| Number of patients with dose interruptions and dose reductions | 4 years | Safety and tolerability |
| Dose intensity | 4 years | Safety and tolerability |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | 4 years | Efficacy will be assessed by Lugano Classification (FDG-PET/CT scans) |
| Best overall response (BOR) rate | 4 years | Efficacy will be assessed by Lugano Classification (FDG-PET/CT scans) |
| Area under curve (AUC) for VAY736 and combination partners | 4 years | PK parameters will be derived from serum concentrations |
| Maximum observed drug concentration after single dose administration (Cmax) for VAY736 and combination partners | 4 years | PK parameters will be derived from serum concentrations |
| Change from baseline in anti-drug antibodies (ADA) | Baseline, 4 years | Blood samples will be collected to detect change in levels of antibodies to VAY736 |
Countries
Australia, China, Germany, Italy, Japan, Singapore, South Korea
Contacts
STUDY_DIRECTORNovartis Institutes of Biomedical Research
Novartis Institutes of Biomedical Research
Outcome results
None listed