NCT01352286 · REGISTRY CONDITION SEARCH

Redirected Auto T Cells for Advanced Myeloma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2019-12-03

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Adverse Events Related to Study Treatment

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outcome · POSTED

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

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outcome · POSTED

Best Objective Response (BOR)

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outcome · POSTED

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

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outcome · POSTED

Peak Persistence of Modified T-cells in the Peripheral Blood

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outcome · POSTED

Marrow Antigen Expression Pre-and Post-infusion

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Myeloma has relapsed, progressed, or failed to respond after at least one prior course of therapy (consisting of at least 2 treatment cycles or months of therapy) * Myeloma has responded partially to initial therapy but a complete response (immunofixation negative and normal serum free light chain) has NOT developed after a minimum of 3 cycles or months of initial therapy * Myeloma has high-risk features as defined by the presence of one or more cytogenetic abnormalities known to confer a poor outcome even after standard auto-transplants: complex karyotype (≥ to 3 abnormalities), t(4;14), t(14;16), del (17) (p13.1), and/or chromosome 13 abnormalities. These patients may be enrolled even while in complete or near-complete remission * Measurable disease on study entry, as defined by quantifiable or detectable levels of serum or urine paraprotein or elevated serum free light chains with abnormal ratio * Patients who are in complete remission at the time of proposed study entry (serum and urine immunofixation consistently negative and normal serum free light chains) are not eligible unless their disease meets the criteria for high-risk as defined in protocol * Ages 18-80 * ECOG performance status 0-2 (unless due solely to bone pain) * Prior to Lenalidomide maintenance phase, all study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist® * Females subjects of childbearing potential must have a negative pregnancy test and both male and female (of childbearing potential) subjects must agree to use reliable methods of contraception during the study. * Lenalidomide treatment phase: able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin) * HLA-A201 patients must have confirmed expression of NY-ESO-1 and/or LAGE. HLA-A2 patients must have the A-201 allele Adequate vital organ function as defined below: * Serum creatinine ≤3.0 mg/dl and not on dialysis * WBC at least 3000/mm³, platelet count at least 100,000/mm³ * SGOT ≤ to 2 x upper limit of normal and bilirubin ≤ to 2.0 mg/dl (unless due to Gilbert's syndrome) * Left ventricular ejection fraction (LVEF) ≥ 45%. A lower LVEF is permissible if a formal cardiologic evaluation reveals no evidence for clinically significant functional impairment * Adequate pulmonary function with mechanical parameters ≥ 40% predicted (FEV1, FVC, TLC, DLCO). Patients who are unable to complete PFTs due to bone pain or fracture must have a high resolution CT scan of the chest and must have acceptable arterial blood gases defined as a room air PO2 greater than 70 mmHg * Patients should have recovered from any toxicities related to prior therapy or at least returned to their baseline level of organ function. * Patients should be off of glucocorticoids for at least 2 weeks and/or other therapies for at least 1 week prior to enrollment Exclusion Criteria: * Pregnant or nursing females * HIV or HTLV-1/2 seropositivity * History of myelodysplasia * History of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy) * Active Hepatitis B (as defined by positive Hepatitis B surface antigen); positive Hepatitis C virus (HCV) antibody is NOT an exclusion * Prior allogeneic transplant * History of severe autoimmune disease requiring steroids or other immunosuppressive treatments * Active immune mediated diseases including: connective tissue diseases, uveitis, sarcoidosis, inflammatory bowel disease, multiple sclerosis * Evidence or history of other significant cardiac, hepatic, renal, ophthalmologic, psychiatric, or gastrointestinal disease which would likely increase the risks of participating in the study * Active bacterial, viral, or fungal infections
healthy Volunteers: false
maximum Age: 80 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Genetic: Autologous Genetically modified T cells
label
Autologous Genetically modified T cells
type
EXPERIMENTAL

interventions

arm Group Labels
Autologous Genetically modified T cells
description
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.
name
Autologous Genetically modified T cells
type
GENETIC

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 25
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Number of Participants with Adverse Events related to study treatment
measure
Adverse Events Related to Study Treatment
time Frame
Day -40 to Year 1 post-treatment

secondary Outcomes

description
Objective Response Rate (ORR) of sCR (stringent complete response), CR (complete response), VGPR (very good partial response), PR (partial response)
measure
Number of Participants With Response Per International Myeloma Working Group (IMWG) 2011 Criteria
time Frame
Change from Baseline at Day 42, 100, 180, 270 and Year 1
description
Number of participants with Best Objective Response of sCR, CR, VGPR, or PR
measure
Best Objective Response (BOR)
time Frame
Best Objective Response prior to initiation of lenalidomide and at Year 1
description
Calculated median DOR, PFS, OS
measure
Duration of Response (DOR), Progression Free Survival (PFS), Overall Survival (OS)
time Frame
DOR: Initial date of response to date of progressive disease or death PFS: Date of first T -cell infusion to earliest date of disease progression of death due to any cause OS: Date of first T-cell infusion to date of death from any cause.
description
Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood
measure
Peak Persistence of Modified T-cells in the Peripheral Blood
time Frame
Post-infusion through Day 42
description
Number of participants with NY-ESO-1 and LAGE or LAGE-1a expression in the marrow post-infusion
measure
Marrow Antigen Expression Pre-and Post-infusion
time Frame
Pre- and post-infusion
description
Number of participants with engraftment in blood and bone marrow
measure
Engraftment of Gene-modified Pentamer+ CD4+ T Cells and CD8+ T Cells
time Frame
Post Treatment

Full study description

brief Summary: 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.
detailed Description: 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.

Source references

references

citation
Stadtmauer EA, Faitg TH, Lowther DE, Badros AZ, Chagin K, Dengel K, Iyengar M, Melchiori L, Navenot JM, Norry E, Trivedi T, Wang R, Binder GK, Amado R, Rapoport AP. Long-term safety and activity of NY-ESO-1 SPEAR T cells after autologous stem cell transplant for myeloma. Blood Adv. 2019 Jul 9;3(13):2022-2034. doi: 10.1182/bloodadvances.2019000194.
pmid
31289029
type
BACKGROUND

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice