Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

All Drugs and Chemicals

Amino Acids

Ibrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Increasing doses of VAY736 in combination with a fixed dose of ibrutinib.

Evaluation of the MTD/RD of the combination of VAY736 and ibrutinib that was identified in dose escalation.

VAY736

ibrutinib

Patients enrolled to the study had chronic lymphocytic leukemia (CLL) and received ibrutinib. Patients have either received ibrutinib for one year without having had a complete response or patients developed a resistance mutation to ibrutinib. This study had two parts, a dose escalation part and a dose expansion part. Patients in the expansion part were enrolled into two arms depending on whether they had ibrutinib resistance mutations present at baseline.

VAY736 in Combination With Ibrutinib in Patients With CLL on Ibrutinib

Phase Ib Open-label Study of VAY736 and Ibrutinib in Patients With Chronic Lymphocytic Leukemia (CLL) on Ibrutinib Therapy

A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications that occurs within the first cycle of treatment during the dose escalation part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher. The duration of one treatment cycle is 28 days.

Number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.

Dose reductions and interruptions to assess the tolerability of the combination of VAY736 and ibrutinib.

Dose intensity is calculated as actual cumulative dose divided by duration of exposure.

Assessment of anti-tumor activity based on investigator assessment per International Working Group - Chronic Lymphocytic Leukemia (IWCLL)

ORR is defined as best overall response (BOR) of complete response (CR) or partial response (PR), assessed by investigators per IWCLL criteria.

TTP is the time from start of treatment to the date of event which is defined as the first documented progression or death due to underlying cancer.

Clearance of ibrutinib resistance mutation is defined as less than 1% mutation bearing alleles (BTKC481 and/or PLCγ2) during treatment.

This endpoint is only applicable to the expansion arm involving chronic lymphocytic leukemia (CLL) patients on ibrutinib with acquired resistance mutations but without clinical relapse.

Plasma pharmacokinetic (PK) parameters calculated using non-compartmental methods.

Number of participants with anti-VAY736 antibodies at baseline and on treatment.

Novartis Pharmaceuticals

Antineoplastic Agents

Antirheumatic Agents

Antibodies

Antibodies, Monoclonal

Rituximab

Immunoglobulins

Immunoglobulins, Intravenous

Ofatumumab

Patients with relapsed/refractory CLL with two or three prior treatment regimens

Patients with relapsed/refractory CLL with four or more prior treatment regimens

VAY736 is a human immunoglobulin of the G class (IgG1/k) monoclonal antibody (mAb) designed to specifically bind the BAFF receptor. VAY736 binds primarily to B-cells through its fragment antigen binding (Fab) region, in human whole blood and spleen samples; it does not bind to natural killer (NK) cells, monocytes, dendritic cells, granulocytes, or platelets.

This study will assess the safety and preliminary efficacy of escalating doses of VAY736 in relapsed or refractory CLL patients.

This Phase 1, multicenter, open-label, study will investigate the safety, pharmacokinetics, pharmacodynamics, and preliminary antil-CLL activity of VAY736 in patients with relapsed/refractory CLL who have received at least two prior regimens. The study will include one arm in the dose escalation phase and two arms in the dose expansion phase.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VAY736 in Relapsed or Refractory CLL Patients

A Phase 1, Muticenter, Open-label, Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VAY736 When Administered Intravenously in Relapsed or Refractory Chronic Lymphocytic Leukemia Patients

Frequency and characteristics of DLTs. Determination of the maximum tolerated dose (MTD) and/or the recommended dose for expansion (RDE) of VAY736 when administered weekly in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) (dose escalation only).

Determine the preliminary anti-CLL (chronic lymphocytic leukemia) activity of VAY736 at the MTD/RDE in patients with relapsed or refractory CLL.

Plasma concentrations to characterize the pharmaconinetics of VAY736

To assess the pharmacodynamics of VAY736.

To assess the safety and tolerability of VAY736 by type, frequency, and severity of AEs, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs, and electrocardiograms.

PK parameters include AUC0-tlast, Cmax, T1/2

To assess the pharmacodynamic effect of VAY736.

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Mantle Cell Lymphoma

Follicular Lymphoma

Marginal Zone Lymphoma

Lenalidomide

Interleukin-4

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

VAY736 single agent dose escalation in patients with NHL subtypes of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL)

VAY736 single agent dose expansion in patients with DLBCL

VAY736 + lenalidomide dose escalation in patients with DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL). Enrollment has been halted in this arm.

VAY736 + lenalidomide dose expansion in patients with DLBCL. This arm will not be conducted.

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.

Immune-modulatory agent that enhances activation of NK cells.

lenalidomide

Novartis Institutes of Biomedical Research

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.

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 will be explored alone or in combination with partner therapies. Increasing doses of VAY736 alone or in combination will be given to small groups of patients to identify the MTD/RD in patients with NHL. In dose expansion, some or all the treatments from dose escalation will be tested at the recommended doses in patients with NHL. Combination partners may be added in the future by protocol amendment. The study is expected to be approximately 4 years in duration (from enrollment of first patient to discontinuation of last patient).

Study of VAY736 as Single Agent and in Combination With Select Antineoplastic Agents in Patients With Non-Hodgkin Lymphoma

A Phase Ib, Multi-center, Open-label Dose Escalation and Expansion Platform Study of VAY736 as Single Agent and in Combination With Select Antineoplastic Agents in Patients With Non-Hodgkin Lymphoma (NHL)

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.

Efficacy will be assessed by Lugano Classification (FDG-PET/CT scans)

PK parameters will be derived from serum concentrations

Blood samples will be collected to detect change in levels of antibodies to VAY736

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
VAY736 in Combination With Ibrutinib in Patients With CLL on Ibrutinib	NCT03400176	Chronic Lymphoc...	VAY736 ibrutinib	18 Years -	Novartis
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VAY736 in Relapsed or Refractory CLL Patients	NCT02137889	Relapsed or Ref...	VAY736	18 Years -	Novartis
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VAY736 in Relapsed or Refractory CLL Patients	NCT02137889	Relapsed or Ref...	VAY736	18 Years -	Novartis
Study of VAY736 as Single Agent and in Combination With Select Antineoplastic Agents in Patients With Non-Hodgkin Lymphoma	NCT04903197	Non-Hodgkin Lym...	VAY736 lenalidomide	18 Years -	Novartis

Spots Global Cancer Trial Database for vay736

Every month we try and update this database with for vay736 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for vay736

Every month we try and update this database with for vay736 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for vay736 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.