Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Lenalidomide

Bortezomib

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

The main study consists of 4 phases a) 28-day screening phase; b) an induction phase inclusive of two 42-day induction treatment cycles: Isatuximab (IV), Bortezomib (SQ). Lenalidomide (PO), Dexamethasone; c) Followed by stem cell mobilization (at the discretion of the Principal Investigator \[PI\]);d) Participants will proceed with either autologous stem cell transplant or two additional induction cycles.

- Induction will be followed by a maintenance phase that continues until disease progression.

Via IV at predetermined dosage and predetermined days during each cycle

Isatuximab

Oral, predetermined dosage and predetermined days during each cycle

SQ Oral, predetermined dosage and predetermined days during each cycle

Bortezomib Injection

IV or Oral predetermined dosage and predetermined days during each cycle

Jacob C Laubach, MD

This research is testing whether the investigational drug isatuximab is safe and effective when used in combination with standard agents for the treatment of newly diagnosed multiple myeloma.

This is a multi-center, single-arm, open-label, Phase 2 study in patients with newly diagnosed multiple myeloma (NDMM) eligible for high dose therapy (HDT) and autologous stem cell transplant (ASCT).

In this research study, investigators are evaluating whether isatuximab is safe and effective in participants with newly diagnosed multiple myeloma when given in combination with lenalidomide, bortezomib, and dexamethsone.

* This research study involves administration of a four-drug chemotherapy regimen that combines the Investigational drug isatuximab with a standard chemotherapy regimen comprised of lenalidomide, bortezomib, and dexamethasone.
* This 4-drug regimen is not considered standard of the treatment of newly diagnosed multiple myeloma.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug or combination of drugs to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The U.S. Food and Drug Administration (FDA) has approved lenalidomide, bortezomib, and dexamethasone as treatment options for this disease but the combination of these agents with isatuximab hasn't been approved.

Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in NDMM

Phase 2, Multi-Center, Single-Arm, Open-Label Study to Evaluate the Efficacy and Safety of the Combination Regimen Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

proportion of patients who have achieved sCR, according to IMWG criteria, by the end of two cycles of induction treatment. Response will be evaluated using a Simon optimal two-stage design.

Progression-free probabilities over time will be estimated using the Kaplan-Meier method (Kaplan, 1958), presenting an estimate of median time to progression (TTP) with 95% confidence intervals (CIs). Time to progression is defined as time from registration to progression, censored at date last known to be progression-free for those who have not progressed and censored at time of death for those who died.

- Progression-free survival (PFS) will be analyzed similarly to time to progression: Progression-free probabilities over time will be estimated using the Kaplan-Meier method (Kaplan, 1958), presenting an estimate of median Time to progression (TTP) with 95% confidence intervals (CIs Time from registration to disease progression or death from any cause, censored at date last known to be progression-free for those who have not progressed or died

Duration of Response will be analyzed similarly to time to progression: Progression-free probabilities over time will be estimated using the Kaplan-Meier method (Kaplan, 1958), presenting an estimate of median time to progression (TTP) with 95% confidence intervals (CIs Time from first response after treatment to the date of disease progression or death from any cause, or date last known progression-free and alive for those who have not progressed or died.

Overall Survival will be analyzed similarly to time to progression: Progression-free probabilities over time will be estimated using the Kaplan-Meier method (Kaplan, 1958), presenting an estimate of median time to progression (TTP) with 95% confidence intervals (CIs

Overall survival: time from registration to death from any cause or date last known alive for those who have not died

Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) v5.0

Sanofi

Jacob Laubach, MD

Sponsor Investigator

Antibodies

Antibodies, Bispecific

Immunoglobulins

Muromonab-CD3

Linvoseltamab dose escalation (part A) and dose expansion (part B) for participants with NDMM who are treatment-naïve.

Transplant-ineligible participants, enrolled in dose expansion, will receive selected Linvoseltamab regimen until disease progression as per protocol.

Transplant-eligible participants, enrolled in dose expansion, will receive selected linvoseltamab regimen for a fixed duration of treatment as per protocol

Linvoseltamab will be administered by intravenous (IV) infusion

Linvoseltamab

Clinical Trials Administrator

Clinical Trial Management

This study is researching an experimental drug called linvoseltamab (called "study drug"). The study is focused on participants with newly diagnosed multiple myeloma (NDMM) who are eligible for high dose chemotherapy with autologous stem cell transplantation (transplant-eligible) or ineligible for autologous stem cell transplantation (transplant-ineligible).

The aim of this clinical trial is to study the safety, tolerability (how the body reacts to the drug), and effectiveness (tumor shrinkage) of linvoseltamab in study participants with NDMM as a first step in determining if the study drug has a role in the treatment of NDMM.

This study consists of 2 phases:

* In Phase 1, the study drug will be given to participants to study the side effects of the study drug and to establish the regimen (initial doses and full dose) of the study drug to be given to participants in Phase 2.
* In Phase 2, the study drug will be given to more participants to continue to assess the side effects of the study drug and to evaluate the ability of the study drug to shrink the tumor (multiple myeloma) in participants with NDMM.

The study is looking at several research questions, including:

* What side effects may happen from taking linvoseltamab?
* What the right dosing regimen is for linvoseltamab?
* How many participants treated with linvoseltamab have improvement of their disease and for how long?
* The effects of linvoseltamab study treatment before and after transplant
* How much linvoseltamab is in the blood at different times?
* Whether the body makes antibodies against linvoseltamab (which could make the drug less effective or could lead to side effects).

Note: Phase 1 part B will be randomized 1:1. All other participants will be non-randomized.

A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment

Phase 1/2 Study of Linvoseltamab (Anti-BCMA X Anti-CD3 Bispecific Antibody) in Previously Untreated Patients With Symptomatic Multiple Myeloma

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in NDMM	NCT04653246	Multiple Myelom... Newly Diagnosed... Autologous Stem...	Isatuximab Lenalidomide Bortezomib Inje... Dexamethasone	75 Years -	Dana-Farber Cancer Institute
Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in NDMM	NCT04653246	Multiple Myelom... Newly Diagnosed... Autologous Stem...	Isatuximab Lenalidomide Bortezomib Inje... Dexamethasone	75 Years -	Dana-Farber Cancer Institute
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment	NCT05828511	Multiple Myelom...	Linvoseltamab	18 Years -	Regeneron Pharmaceuticals
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment	NCT05828511	Multiple Myelom...	Linvoseltamab	18 Years -	Regeneron Pharmaceuticals

Spots Global Cancer Trial Database for newly diagnosed multiple myeloma (ndmm)