Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Monoclonal Gammopathy of Undetermined Significance

Smoldering Multiple Myeloma

Paraproteinemias

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Hypergammaglobulinemia

Precancerous Conditions

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Immunoglobulins

Immunoglobulins, Intravenous

Myeloma Proteins

Paraproteins

Sequential groups of participants will be enrolled to assess the initial safety and tolerability of the step-up regimen leading up to the start of different full doses of linvoseltamab.

Participants will be randomized in a 1:1:1:1 ratio across 4 dosing regimens

Administration by intravenous (IV) infusion

Linvoseltamab

Clinical Trials Administrator

Clinical Trial Management

The primary purpose of the study is to understand how well the study drug can eliminate abnormal plasma cells and laboratory signs of high-risk monoclonal gammopathy of undetermined significance (HR-MGUS) and non high-risk smoldering multiple myeloma (NHR-SMM). This requires understanding the safety and tolerability of the study drug (how the body reacts to linvoseltamab) as well as the effectiveness of the study drug (how well linvoseltamab eliminates plasma cells). All participants will start treatment with gradually increasing doses of linvoseltamab (step-up doses) before they start receiving the assigned full dose.

The study is split into 2 parts:

* In Part 1, separate groups of 3-6 patients will receive different full doses of linvoseltamab to evaluate the short-term side effects (safety) and tolerability of the study drug within the first 5 weeks after starting treatment. The data collected will help to make a decision about the dosing regimens chosen for Part 2.
* In Part 2, a larger number of participants will be randomized to different dosing regimens to further assess the side effects of linvoseltamab, and to evaluate the ability of linvoseltamab to eliminate abnormal plasma cells in HR-MGUS and NHR-SMM.

The study is looking at several other research questions, including:

* How many participants treated with linvoseltamab have improvement of their HR-MGUS or NHR-SMM?
* What side effects may happen from taking the study drug?
* How much study drug is in the blood at different times?
* Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects).

A Proof-of-Concept Study to Learn Whether Linvoseltamab Can Eliminate Abnormal Plasma Cells That May Lead to Multiple Myeloma in Adult Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma

Phase 2 Dose-Ranging and Interception Study of Linvoseltamab in Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

Part 1 As assessed by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading system version 5 (for all grades). AESI include grade 2 or higher cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), grade 3 or higher tumor lysis syndrome (TLS), infusion-related reaction (IRR), allergic reactions, infections and hepatitis B virus (HBV) reactivation

Part 1 As assessed by the NCI-CTCAE grading system version 5 (for all grades)

As assessed by the NCI-CTCAE grading system version 5 (for all grades)

Regeneron Pharmaceuticals

Syndrome

Leukemia

Preleukemia

Myelodysplastic Syndromes

Lymphoma

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Graft Versus Host Disease

Lymphosarcoma

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Anti-Infective Agents

Plerixafor

Medical Monitor

Genzyme will evaluate/monitor the off label transplant use of plerixafor using data in the European Group for Blood and Marrow Transplantation (EBMT) registry. Off-label use of plerixafor will be collected for data entered over a 5 year time span (i.e., data entered into the registry between the date of European Union (EU) marketing authorization \[31 July 2009\] and 31 July 2014).

The EBMT is a non-profit, scientific society representing more than 600 transplant centers mainly in Europe. The EBMT promotes all activity aiming to improve stem cell transplantation or cellular therapy, which includes registering all the activity relating to stem cell transplants. Data are entered, managed, and maintained in a central database with internet access; each EBMT center is represented in this database.

The collection by the EBMT registry of reasons for the off-label transplant use of plerixafor shall provide information of a substantial number of patients who are representative of the patient population receiving plerixafor off-label.

Analysis of Data Collected in the European Group for Blood and Marrow Transplantation (EBMT) Registry for Off-Label Transplant Use of Plerixafor

Monitoring of Plerixafor Off-Label Use in the European Group for Blood and Bone Marrow Transplantation (EBMT) Registry

European Society for Blood and Marrow Transplantation

Genzyme, a Sanofi Company

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Proof-of-Concept Study to Learn Whether Linvoseltamab Can Eliminate Abnormal Plasma Cells That May Lead to Multiple Myeloma in Adult Patients With High-Risk Monoclonal Gammopathy of Undetermined Significance or Non-High-Risk Smoldering Multiple Myeloma	NCT06140524	Monoclonal Gamm... Smoldering Mult...	Linvoseltamab	18 Years -	Regeneron Pharmaceuticals
Analysis of Data Collected in the European Group for Blood and Marrow Transplantation (EBMT) Registry for Off-Label Transplant Use of Plerixafor	NCT01362985	Acute Leukemia Chronic Leukemi... Myelodysplastic... Myeloproliferat... Solid Tumors Lymphoma Plasma Cell Dis...		- 18 Years	Sanofi

Spots Global Cancer Trial Database for plasma cell disorders