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

Muromonab-CD3

Patients with advanced myeloma and who are candidates for autologous stem cell transplants, or syngeneic stem cell transplants (SSCT), will be eligible. Prior to full screening on this study, patients will undergo prescreening to evaluate HLA-A type and presence of NY-ESO-1c259T/LAGE antigen. Patients will undergo a steady-state mononuclear cell apheresis for T cell collection, with an optional second collection. Once mononuclear cells have been collected, patients (or donors in the case of SSCT) will then undergo hematopoietic stem cell mobilization. Patients will receive a dose \>0.1-1 x 10¹º anti-CD3/anti-CD28-costimulated autologous T cells which have been genetically modified to express high affinity NY-ESO-1c259 TCRs.

Patients will undergo myeloma restaging at days +42, +100, 6 months, 9 months and 1 year post infusion. At this point, in accordance with FDA Guidelines, all patients will enter long term follow up (LTFU) and be followed biannually for monitoring for gene transfer delayed adverse events until year 5 post infusion. From year 5, all patients will require annual LTFU visits for monitoring for delayed adverse events until year 15 after receiving the genetically modified T cells.

Patients whose disease progresses prior to year 1 will enter LTFU at time of progression; however these patients will be seen quarterly from progression until year 1 post infusion and then follow the LTFU schedule mentioned above.

Autologous Genetically modified T cells

GSK Clinical Trials

The purpose of this study is to 1) evaluate the safety and tolerability of autologous genetically modified T cells transduced to express the high affinity NY-ESO-1c259 TCR in HLA-A2+ subjects and 2) measure the incidence of GVHD in patients following infusion of TCR modified autologous T cells.

The primary objective of this study is to evaluate the safety and tolerability of autologous genetically modified T cells. Genetic material is transferred into the subject's previously harvested autologous T cells to redirect them to target myeloma cells rather than their usual target. Study subjects must have systemic or multifocal myeloma requiring autologous stem cell transplantation whose disease has relapsed or incompletely responded to prior therapy or have high-risk features. Subjects must also have measureable disease on study entry, as defined by quantifiable or detectable levels of serum or urine paraprotein or elevated serum free light chains with an abnormal ratio.

Redirected Auto T Cells for Advanced Myeloma

A Phase I/IIa, Dual-cohort, Two-site, Clinical Trial Evaluating the Safety and Activity of Redirected Autologous T Cells Expressing a High Affinity TCR Specific for NY-ESO-1 Administered Post ASCT in Patients With Advanced Myeloma

IPD for this study will be made available via the Clinical Study Data Request site.

Number of Participants with Adverse Events related to study treatment

Objective Response Rate (ORR) of sCR (stringent complete response), CR (complete response), VGPR (very good partial response), PR (partial response)

Number of participants with Best Objective Response of sCR, CR, VGPR, or PR

Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood

Number of participants with NY-ESO-1 and LAGE or LAGE-1a expression in the marrow post-infusion

Number of participants with engraftment in blood and bone marrow

GlaxoSmithKline

Participants who received NY-ESO-1ᶜ²⁵⁹T following ASCT

Participants who received NYESO-1ᶜ²⁵⁹T following ASCT

NYESO-1ᶜ²⁵⁹T Cells

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

GSK Response Center

Adverse Events Related to Study Treatment

Day 42

Day 100

Day 180

Day 270

Year 1

Number of Participants With Response Per International Myeloma Working Group (IMWG) 2011 Criteria

Prior to Initiation of Lenalidomide : sCR

Prior to Initiation of Lenalidomide : CR

Prior to Initiation of Lenalidomide : VGPR

Prior to Initiation of Lenalidomide : PR

Year 1 : sCR

Year 1 : CR

Year 1 : VGPR

Year 1 : PR

Participants who received NYESO-1ᶜ²⁵⁹T following ASCT with Best Objective Response (BOR) data.

Best Objective Response (BOR)

Duration of Response (DOR), Progression Free Survival (PFS), Overall Survival (OS)

Peak Persistence of Modified T-cells in the Peripheral Blood

Day 100 : NY-ESO-1

Day 100 : LAGE or LAGE-1a

Day 180 : NY-ESO-1

Day 180 : LAGE or LAGE-1a

Participants who received NYESO-1ᶜ²⁵⁹T following ASCT with data at pre-and post-infusion time points

Participants who received NYESO-1ᶜ²⁵⁹T following ASCT with expression data at all points.

Marrow Antigen Expression Pre-and Post-infusion

CD4+ : Blood

CD4+ : Bone Marrow

CD8+ : Blood

CD8+ : Bone Marrow

Participants who received NYESO-1ᶜ²⁵⁹T following ASCT with engraftment data.

Engraftment of Gene-modified Pentamer+ CD4+ T Cells and CD8+ T Cells

Participants who received lentivirus-mediated genetically engineered NYESO-1ᶜ²⁵⁹T following autologous stem cell transplantation (ASCT)

Spots Global Cancer Trial Database for Redirected Auto T Cells for Advanced Myeloma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial