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

All Drugs and Chemicals

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

Regeneron Pharmaceuticals

Lymphoma

Lymphoma, Mantle-Cell

Lymphatic Diseases

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Anti-Infective Agents

Antibodies, Monoclonal

Dexamethasone

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Rituximab

Vincristine

Lenograstim

Bortezomib

Dexamethasone acetate

BB 1101

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Adjuvants, Immunologic

Tubulin Modulators

Antimitotic Agents

VcR-CVAD induction: Patients receive VcR-CVAD comprising bortezomib IV over 3-5 seconds on days 1 and 4; rituximab IV over 3-4 hours on day 1; doxorubicin hydrochloride IV over 48 hours on days 1 and 2; cyclophosphamide IV over 3 hours every 12 hours on days 1-3; vincristine IV over 3-5 seconds on day 3; and dexamethasone IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) subcutaneously (SC) or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Maintenance rituximab: Beginning 4-8 weeks after completion of induction therapy, patients receive rituximab IV over 3-4 hours once weekly for 4 weeks. Treatment repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity.

VcR-CVAD induction: Patients receive VcR-CVAD comprising bortezomib IV over 3-5 seconds on days 1 and 4; rituximab IV over 3-4 hours on day 1; doxorubicin hydrochloride IV over 48 hours on days 1 and 2; cyclophosphamide IV over 3 hours every 12 hours on days 1-3; vincristine IV over 3-5 seconds on day 3; and dexamethasone IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) SC or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

ASCT: After completion of induction therapy, patients who are eligible may have the option to receive consolidation therapy for autologous stem cell transplantation (off-study). These patients undergo stem cell harvest during courses 4, 5, or 6 of induction therapy.

bortezomib

rituximab

cyclophosphamide

doxorubicin hydrochloride

vincristine

dexamethasone

filgrastim

pegfilgrastim

Autologous stem cell transplantation (ASCT)

Brad Kahl

This phase II trial is studying how well giving rituximab together with combination chemotherapy and bortezomib works in treating patients with untreated mantle cell lymphoma. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving rituximab together with combination chemotherapy and bortezomib may kill more cancer cells.

Treatment consists of six agents: bortezomib (Vc), rituximab (R), cyclophosphamide (C), vincristine (V), doxorubicin (A), and dexamethasone (D) (VcR-CVAD).

PRIMARY OBJECTIVES:

I. To evaluate the complete response (CR) rate in patients with mantle cell lymphoma, who are treated with VcR-CVAD.

SECONDARY OBJECTIVES:

I. To evaluate the overall response rate to VcR-CVAD. II. To evaluate the progression-free survival (PFS) and overall survival (OS) of patients receiving maintenance rituximab after VcR-CVAD induction.

III. To evaluate the PFS and OS of patients who receive autologous stem cell transplantation (ASCT) after VcR-CVAD induction.

IV. To evaluate the toxicity of VcR-CVAD.

TERTIARY OBJECTIVES:

I. Evaluation of antigen expression patterns to determine or confirm possible unique expressions of MCL.

II. To evaluate the percentage of circulating mantle cell lymphoma (MCL) cells.

OUTLINE: This is a multicenter study.

Induction therapy (VcR-CVAD): Patients receive VcR-CVAD comprising bortezomib 1.3 mg/m2 IV over 3-5 seconds on days 1 and 4; rituximab 375 mg/m2 IV over 3-4 hours on day 1; doxorubicin hydrochloride 25 mg/m2/d IV over 48 hours on days 1 and 2; cyclophosphamide 300 mg/m2 IV over 3 hours every 12 hours on days 1-3; vincristine 1 mg IV over 3-5 seconds on day 3; and dexamethasone 40 mg IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) subcutaneously (SC) or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Maintenance therapy: Beginning 4-8 weeks after completion of induction therapy, patients receive rituximab IV over 3-4 hours once weekly for 4 weeks. Treatment repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of induction therapy, patients who are eligible may have the option to receive consolidation therapy for autologous stem cell transplantation (ASCT) (off-study). These patients undergo stem cell harvest during courses 4, 5, or 6 of induction therapy.

After completion of study treatment, patients are followed periodically for up to 10 years.

Combination Chemotherapy and Rituximab in Treating Patients With Untreated Mantle Cell Lymphoma

A Phase II Study of VcR-CVAD With Rituximab Maintenance for Untreated Mantle Cell Lymphoma

Number of eligible, treated participants who achieve complete response. Response criteria are based upon the criteria from the Revised Response Criteria for Malignant Lymphoma (Cheson et al., 2007). Complete response is defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy.

PFS for patients who received maintenance rituximab or ASCT after VcR-CVAD induction is defined as time from start of maintenance rituximab or ASCT to earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored.

OS for patients who received maintenance rituximab or ASCT after VcR-CVAD induction is defined as time from start of maintenance rituximab or ASCT to death. Patients alive at last follow-up were censored.

National Cancer Institute (NCI)

Autologous stem cell transplantation (ASCT) was optional for this study, and submission of data with details on conditioning regimen or toxicity was not mandated. Therefore, the adverse event table for ASCT arm was not available.

All patients who received VcR-CVAD induction.

Step 1 - VcR-CVAD Induction

All patients who received maintenance rituximab.

Step 2 - Maintenance Rituximab

All eligible patients who received VcR-CVAD induction.

Age, Continuous

Sex: Female, Male

Study Statistician

VcR-CVAD Induction

Complete Response (CR) Rate

VcR-CVAD induction: Patients receive VcR-CVAD comprising bortezomib IV over 3-5 seconds on days 1 and 4; rituximab IV over 3-4 hours on day 1; doxorubicin hydrochloride IV over 48 hours on days 1 and 2; cyclophosphamide IV over 3 hours every 12 hours on days 1-3; vincristine IV over 3-5 seconds on day 3; and dexamethasone IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) SC or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Maintenance rituximab: Beginning 4-8 weeks after completion of induction therapy, patients receive rituximab IV over 3-4 hours once weekly for 4 weeks. Treatment repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity.

VcR-CVAD Induction Followed by Maintenance Rituximab

VcR-CVAD Induction Followed by ASCT

Eligible and treated patients who received maintenance rituximab or ASCT

2-year Progression-free Survival (PFS)

3-year Overall Survival (OS)

VcR-CVAD induction: Patients receive VcR-CVAD comprising bortezomib IV over 3-5 seconds on days 1 and 4; rituximab IV over 3-4 hours on day 1; doxorubicin hydrochloride IV over 48 hours on days 1 and 2; cyclophosphamide IV over 3 hours every 12 hours on days 1-3; vincristine IV over 3-5 seconds on day 3; and dexamethasone IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) subcutaneous (SC) or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Maintenance rituximab: Beginning 4-8 weeks after completion of induction therapy, patients receive rituximab IV over 3-4 hours once weekly for 4 weeks. Treatment repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients received VcR-CVAD induction but did not proceed to step 2 treatment for various reasons.

VcR-CVAD Induction Then Off Study

Step 2 - Maintenance Rituximab or ASCT

Lymphoma, B-Cell

B-cell Lymphoma

Bendamustine Hydrochloride

Melphalan

This is a phase I study of rituximab, bendamustine and melphalan (RBM) conditioning followed by ASCT in elderly patients with B-cell NHL. Conditioning regimen consist of rituximab 375 mg/m2 on days -11 and -4, bendamustine 160 mg/m2 intravenously on days -3 and -2; melphalan 140 mg/m2 intravenously on day -1 before the reinfusion of autologous stem cells on day 0. The conditioning timeline can be modified if there are patient scheduling conflicts. Patients who are deemed inevaluable will be replaced for the primary objective. Patients will be considered inevaluable if they don't receive one dose of conditioning regimen and are removed from the study.

rituximab 375 mg/m2 on days -11 and -4, The second dose of rituximab (day -4) is administered 7 days after the first dose (day -11), +/- 1 day. Rituximab may be administered by a local oncologist. If the participant has a CD20 negative tumor, rituximab can be omitted from the conditioning regimen.

bendamustine 160 mg/m2 intravenously on days -3 and -2

bendamustine

melphalan 140 mg/m2 intravenously on day -1 before the reinfusion of autologous stem cells on day 0.

melphalan

reinfusion of autologous stem cells on day 0.

Autologous Stem Cell Transplantation (ASCT)

Parastoo Dahi, MD

This study is testing a combination of chemo-immuno therapy called RBM. RBM consists of combination of drugs: rituximab, bendamustine, and melphalan followed by reinfusion of the participants own stem cells which is called autologous stem cell transplant (ASCT). Compared to the standard BEAM regimen, this RBM regimen may or may not be less effective in lymphoma, but will likely have fewer side effects.

This is a phase I single arm, open label trial

A Phase I Study of Bendamustine and Melphalan Conditioning and Autologous Stem Cell Transplantation for Treatment of Multiple Myeloma and Relapsed/Refractory B-cell Lymphoma in Elderly Patients

are defined as grade \> 3, non-hematologic toxicity related to treatment excluding grade 3 nausea or vomiting responsive to anti-emetic treatment, grade 3 diarrhea responding to anti-diarrheal treatment, grade 3 fatigue, grade 3 skin rash responsive to topical or systemic steroids, grade 3 fevers (\> 40 degrees Celsius for \< 24 hours) and alopecia per CTCAE

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
Combination Chemotherapy and Rituximab in Treating Patients With Untreated Mantle Cell Lymphoma	NCT00433537	Contiguous Stag... Noncontiguous S... Stage I Mantle ... Stage III Mantl... Stage IV Mantle...	bortezomib rituximab cyclophosphamid... doxorubicin hyd... vincristine dexamethasone filgrastim pegfilgrastim Autologous stem...	18 Years -	National Cancer Institute (NCI)
A Phase I Study of Bendamustine and Melphalan Conditioning and Autologous Stem Cell Transplantation for Treatment of Multiple Myeloma and Relapsed/Refractory B-cell Lymphoma in Elderly Patients	NCT03352765	Lymphoma	rituximab bendamustine melphalan Autologous Stem...	65 Years -	Memorial Sloan Kettering Cancer Center
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 autologous stem cell transplantation (asct)