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

Participants will undergo apheresis to collect cells to make SLAMF7 fresh peripheral blood mononuclear cells (FPBMC). These cells will be activated in the lab to fight against multiple myeloma. About 3-4 days after apheresis, participants will start receiving infusions of SLAMF7 FPBMC. Throughout treatment, participants will have blood taken for labs, to check disease status and also to look at immune response. Study treatment will stop if the participant has disease progression.

Participants will receive 8 weekly infusions of SLAMF7 FPBMC, then 8 additional infusions every 2 weeks.

SLAMF7 FPBMC

Laahn Foster, MD

The purpose of this study is to understand the safety and estimate the efficacy of combining anti-CD3 x anti-SLAMF7 bispecific antibody fresh peripheral blood mononuclear cells (SLAMF7 FPBMC/CS1 FPBMC) for patients with relapsed and/or refractory multiple myeloma. Patients receive 8 weekly doses and then 8 more doses every 2 weeks of SLAMF7 FPBMC by intravenous infusion.

Once subjects are determined eligible, white blood cells (lymphocytes) are collected via leukapheresis procedure. The white blood cells, specifically T cells, are then mixed with two proteins, OKT3 and IL-2, which activate the cells to multiply.

The "activated" T cells are coated with the OKT3 and elotuzumab (an anti-SLAMF7 drug) to produce bispecific fresh peripheral blood mononuclear cells (FPBMC).

About 72 hours after the leukapheresis procedure, SLAMF7 FPBMC infusions will start. After about 8-9 weeks, participants will have another leukapheresis procedure and then receive doses every 2 weeks for 8 more doses. Before, throughout and following SLAMF7 FPBMC, research blood will be collected to better understand immune response. Disease status will be checked regularly during and after study treatment.

Phase I/II Study of SLAMF7 FPBMC/CS-1 FPBMC in Relapsed/Refractory Multiple Myeloma

Phase I/II Study of Anti-CD3 x Anti-SLAMF7 (Anti-CS-1) Bispecific Antibody Armed Fresh Peripheral Blood Mononuclear Cells (SLAMF7 FPBMC) in Relapsed/Refractory Multiple Myeloma

An adverse event that is considered at least possibly related to SLAMF7 FPBMC and meets at least one of the protocol-defined criteria

Severity, frequency, category, seriousness and duration of adverse events

As defined by International Myeloma Working Group (IMWG) response criteria (partial response (PR), very good partial response (VGPR), complete response (CR), stringent CR (sCR)

Assessed by ClonoSeq, only for patients who achieve stringent CR or CR

Duration of time from consent through death or 3 years after first FPBMC infusion

IFN-gamma Elispots stimulated by a multiple myeloma cell line

Duration of time from consent through first progression (or end of follow-up)

Anti-SOX2 IgG antibodies in the serum by specific ELISA

T cell count and count for T cell subpopulations

University of Virginia

Associate Progessor

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Nervous System Diseases

Breast Neoplasms

Neoplasm Metastasis

Meningeal Carcinomatosis

Breast Diseases

Skin Diseases

Neoplastic Processes

Meningeal Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Immunomodulating Agents

Approximately 4 weeks following registration and blood collection, participants are given a test dose of HER2 BATs followed by 8 weekly infusions. Infusions are given intraventricularly.

A test dose (1 million cells) of HER2 BATs (at one of the two dose levels: 5 million cells or 10 million cells per infusion) followed by 8 weekly infusions of Her2 BATs delivered into the ventricle of the brain. Infusions are delivered weekly over 8 weeks with brain MRIs prior to first infusion and following the eighth infusion. Blood will be drawn for immune evaluation before during and after study treatment.

HER2 BATs

Camilo Fadul, MD

This study uses bi-specific antibody (HER2Bi) armed activated T-cells (HER2 BATs) to target breast cancer cells that have metastasized to the membranes surrounding the brain and spinal cord. This is known as leptomeningeal metastases. Two doses will be evaluated in order to determine a safe dose.

Study treatment includes a test dose of HER2 BATs followed by 8 weekly infusions of HER2 BATs at the assigned dose level. Before, during and after study treatment, participants will be monitored objectively by brain MRIs and clinically through physical and neurological exams, and blood and cerebrospinal fluid will be collected to evaluate immune responses.

Once subjects are determined eligible, white blood cells (lymphocytes) are collected via leukapheresis procedure approximately 3 to 4 weeks prior to the first BATs infusion. The white blood cells, specifically T cells, are then mixed with two proteins in order to activate the cells to multiply.

After approximately 14 days in culture, the activated T cells are coated with OKT3 and trastuzumab/Herceptin (HER2Bi), and washed to remove excess Herceptin in order to produce bispecific antibody armed T cells (BATs). Cells are then frozen and stored until scheduled to be infused.

Up to 2 weeks following leukapheresis, participants will undergo surgery to place the catheter/reservoir into the lateral ventricle of the brain to allow intraventricular administration of HER2 BATs and a chemotherapy agent methotrexate. A few weeks later, participants will receive the intraventricular methotrexate in order to control disease while the BATs product is being manufactured. About 4-5 weeks following the leukapheresis and at least 7 days after receiving methotrexate, study treatment will begin with a test dose of HER2 BATs. If this dose is well tolerated by the participant, she will then receive 8 weekly doses of HER2 BATs at the assigned dose level.

BATs in Patients With Breast Cancer and Leptomeningeal Metastases

A Phase I Study of Anti-CD3 x Anti-Her2/Neu (Her2Bi) Armed Activated T Cells (ATC) in Patients With Breast Cancer Leptomeningeal Metastases

Types of any adverse events or abnormalities of laboratory tests

Frequency of any adverse events or abnormalities of laboratory tests

Severity of any adverse events or abnormalities of laboratory tests

Timing of onset of any adverse events or abnormalities of laboratory tests

Duration of any adverse events or abnormalities of laboratory tests

Relationship to study therapy of any adverse events or abnormalities of laboratory tests

If at least 80% of the planned dose of cells cannot be produced for 3 consecutive participants at a designated dose level, that dose level will be considered not feasible.

Immune shift induced by Her2 BATs as detected by in vitro cytotoxicity assays and/or IFN-γ EliSpots against breast cancer cell lines

Immune shift induced by Her2 BATs as detected by phenotyping of activating and regulatory immune cells

Immune shift induced by Her2 BATs as detected by measurement of cytokine patterns

Immune shift induced by Her2 BATs as detected by determination of anti-Her2 antibodies

Correlation individually and by heatmap analysis of imaging, pathology, clinical, and immune response characteristics to progression free survival (PFS)

Correlation individually and by heatmap analysis of imaging, pathology, clinical, and immune response characteristics to overall survival (OS).

Proportion of participants with complete or partial response according to brain and spine MRI

Length of time from study participation initiation through disease progression for each participant

Length of time from study participation initiation through death or for 2 years following study treatment for each participant

The MDASI- SP is a 24 item questionnaire that focuses on symptoms related to spinal tumors. For each potential symptom, there is an eleven-point scale where 0 is "Not Present" and 10 is "As Bad As You Can Imagine" so the minimum score would be 0 and the maximum score would be 240. For a subset of questions, the scale measures how much the symptoms interfered with other parts of life and the scale ranges from symptoms that "Did Not Interfere" (0) to those that "Interfered Completely" (10). Lower scores indicate fewer/less severe/less interfering symptoms and higher scores indicate more/more severe/more interfering symptoms.

The MDASI- BT is a 28 item questionnaire that focuses on symptoms related to brain tumors. For each potential symptom, there is an eleven-point scale where 0 is "Not Present" and 10 is "As Bad As You Can Imagine" so the minimum score would be 0 and the maximum score would be 280. For a subset of questions, the scale measures how much the symptoms interfered with other parts of life and the scale ranges from symptoms that "Did Not Interfere" (0) to those that "Interfered Completely" (10). Lower scores indicate fewer/less severe/less interfering symptoms and higher scores indicate more/more severe/more interfering symptoms.

Professor

Lymphoma

Lymphoma, Follicular

Lymphatic Diseases

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

Myriem Chikhaoui, Msc

Juliette V Diou, PhD

Jean-Baptiste Robin, MD

FRANCK MORSCHHAUSER, MD

Jean Marc Schiano de Colella

Jean Marc Schiano de Colella, MD

Guillaume Cartron, MD

Benoit Tessoulin, MD

Agathe Waultier-Rascalou, MD

Remy DULERY, MD

Stéphanie Guidez, MD

Roch Houot, MD

Camille Laurent, MD

Karin Tarte, PhD

Franck MORSCHHAUSER, MD

Mosunetuzumab is a T-cell bispecific antibody targeting CD20 and CD3 aiming to redirect T cells to engage and eliminate malignant B cells. Bispecific antibodies (BsAb) are a promising treatment option which can induce long-term responses in refractory and relapsed B cell lymphoma patients. However, the factors determining the quality and duration of responses are poorly understood.

the objective is to produce a collection of great scientific interest for lymphoma research from CELESTIMO's clinical trial patients' samples to increase knowledge of treatment with mosunetuzumab's for patients with follicular lymphoma (FL).

study population involves patients participating to CELESTIMO study in France. 10 sites are expected in this biobanking protocol study

Biological samples will collected as part of routine care (tissue and blood already sampled in routine and/or CELESTIMO study) at screening, at C4, at C12 or at progressive disease/relapse.

* Lymph node biopsies: Cryostor, Formalin-Fixed, Paraffin-Embedded (FFPE), and frozen
* Whole blood
* Bone marrow aspiration

Signatures of Response and Resistance to Mosunetuzomab in Follicular Lymphomas (FL)

Roche Pharma AG

The Lymphoma Academic Research Organisation

Recurrence

Osteosarcoma

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Gaucher Disease Type 2

Neuroepithelioma

Anti-Infective Agents

Antineoplastic Agents

Analgesics

Sargramostim

Aldesleukin

Interleukin-2

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Patients receive IL-2 SC daily on days -2 to 35, GM-CSF SC twice weekly x 5 weeks, and GD2Bi-aATC IV over 30 minutes twice weekly x 4 weeks for a total of 8 infusions. Laboratory evaluations of immune responses are obtained prior and after immunotherapy.

IL-2

GD2Bi-aATC

GM-CSF

laboratory evaluations of immune responses

Holly Davis

Maxim Y. Yankelevich, MD

Diana Gomez, MPH

Shakeel Modak, M.D.

Alexandar Chou, M.D.

Daniel (Trey) Lee, MD

Maxim Yankelevich

Previous research has demonstrated that investigators can coat (arm) T cells with a special molecule called GD2 bispecific antibody that will help T cells recognize neuroblastoma and osteosarcoma cells and kill them. This bispecific antibody recognizes GD2, a protein found on almost all neuroblastoma and osteosarcoma cells. The investigators put the GD2 bispecific antibody on T cells and give large numbers of these T cells back to patients. The investigators think that these T cells may have a better chance of killing GD2 expressing tumor cells when they are armed with GD2 bispecific antibody. This trial studies the side effects and best dose of activated T cells armed with GD2 bispecific antibody and how well they work in treating patients with neuroblastoma, osteosarcoma, and other GD2-positive solid tumors.

PRIMARY OBJECTIVES:

I. To perform a phase I dose-escalation study in patients with recurrent or refractory neuroblastoma (NB) and other GD2-positive tumors to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) for anti-CD3 x hu3F8 bispecific antibody (GD2Bi)-armed activated T cells (aATC) infused twice a week for a total of eight infusions in combination with daily IL-2 (300,000 IU/m\^2/day) and GM-CSF (250 ug/m\^2 twice per week) in a standard 3 + 3 dose escalation schema with 40, 80, and 160 x 10\^6 cells/kg/infusion dose levels.

II. To conduct a phase II clinical trial to explore efficacy and confirm the toxicity profile of GD2Bi-aATC combined with IL-2 and GM-CSF in a phase II expansion cohort of 22 patients with neuroblastoma (NB) using MTD determined in the phase I.

SECONDARY OBJECTIVES:

I. Evaluate immune responses in the phase I/II trial by sequential monitoring of anti-NB cytotoxicity of peripheral blood lymphocytes and IFN-gamma EliSpots directed at NB lines.

II. To evaluate persistence of aATC in the blood and tumor biopsies by staining for murine IgG2a to confirm trafficking of armed T cells to tumor.

III. To conduct exploratory study of (18F FDG) positron emission tomography (PET)/computed tomography (CT) after armed ATC infusions in selected patients with PET/CT measurable soft tissue and skeletal lesions.

OUTLINE: This is a phase I, dose-escalation study of OKT3/humanized 3F8 bispecific antibody-aATC followed by a phase II study.

Patients receive IL-2 subcutaneously (SC) daily on days -2 to 35, sargramostim SC twice weekly for 4 weeks, and OKT3/humanized 3F8 bispecific antibody-aATC intravenously (IV) over 30 minutes twice weekly for 4 weeks.

After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months.

Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma

Treatment of Neuroblastoma and GD2-Positive Tumors With Activated T Cells Armed With OKT3 X Humanized 3F8 Bispecific Antibodies (GD2Bi): A Phase I/II Study

Safety of GD2Bi-aATC infusions is evaluated to determine MTD

Objective response rate to GD2Bi-aATC infusions

In vitro anti-tumor activity of patients' lymphocytes; changes in cytokine profile; changes in lymphocyte phenotypes

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I/II Study of SLAMF7 FPBMC/CS-1 FPBMC in Relapsed/Refractory Multiple Myeloma	NCT04864522	Multiple Myelom...	SLAMF7 FPBMC	18 Years -	University of Virginia
BATs in Patients With Breast Cancer and Leptomeningeal Metastases	NCT03661424	Breast Cancer F... Leptomeningeal ...	HER2 BATs	18 Years -	University of Virginia
Signatures of Response and Resistance to Mosunetuzomab in Follicular Lymphomas (FL)	NCT05529524	Follicular Lymp...		18 Years -	The Lymphoma Academic Research Organisation
Activated T Cells Armed With GD2 Bispecific Antibody in Children and Young Adults With Neuroblastoma and Osteosarcoma	NCT02173093	Disseminated Ne... Recurrent Neuro...	IL-2 GD2Bi-aATC GM-CSF laboratory eval...	13 Months - 29 Years	University of Virginia
Phase I/II Study of SLAMF7 FPBMC/CS-1 FPBMC in Relapsed/Refractory Multiple Myeloma	NCT04864522	Multiple Myelom...	SLAMF7 FPBMC	18 Years -	University of Virginia

Spots Global Cancer Trial Database for bispecific antibodies