- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT01352286
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
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 2
Kontakter och platser
Studieorter
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Maryland
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Baltimore, Maryland, Förenta staterna, 21201
- GSK Investigational Site
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Pennsylvania
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Philadelphia, Pennsylvania, Förenta staterna, 19104
- GSK Investigational Site
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Experimentell: Autologous Genetically modified T cells
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.
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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. |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Adverse Events Related to Study Treatment
Tidsram: Day -40 to Year 1 post-treatment
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Number of Participants with Adverse Events related to study treatment
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Day -40 to Year 1 post-treatment
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Number of Participants With Response Per International Myeloma Working Group (IMWG) 2011 Criteria
Tidsram: Change from Baseline at Day 42, 100, 180, 270 and Year 1
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Objective Response Rate (ORR) of sCR (stringent complete response), CR (complete response), VGPR (very good partial response), PR (partial response)
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Change from Baseline at Day 42, 100, 180, 270 and Year 1
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Best Objective Response (BOR)
Tidsram: Best Objective Response prior to initiation of lenalidomide and at Year 1
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Number of participants with Best Objective Response of sCR, CR, VGPR, or PR
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Best Objective Response prior to initiation of lenalidomide and at Year 1
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Duration of Response (DOR), Progression Free Survival (PFS), Overall Survival (OS)
Tidsram: 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.
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Calculated median DOR, PFS, OS
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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.
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Peak Persistence of Modified T-cells in the Peripheral Blood
Tidsram: Post-infusion through Day 42
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Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood
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Post-infusion through Day 42
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Marrow Antigen Expression Pre-and Post-infusion
Tidsram: Pre- and post-infusion
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Number of participants with NY-ESO-1 and LAGE or LAGE-1a expression in the marrow post-infusion
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Pre- and post-infusion
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Engraftment of Gene-modified Pentamer+ CD4+ T Cells and CD8+ T Cells
Tidsram: Post Treatment
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Number of participants with engraftment in blood and bone marrow
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Post Treatment
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Samarbetspartners och utredare
Sponsor
Publikationer och användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Hjärt-kärlsjukdomar
- Kärlsjukdomar
- Immunsystemets sjukdomar
- Neoplasmer efter histologisk typ
- Neoplasmer
- Lymfoproliferativa störningar
- Immunproliferativa störningar
- Hematologiska sjukdomar
- Hemorragiska störningar
- Hemostatiska störningar
- Paraproteinemier
- Blodproteinstörningar
- Multipelt myelom
- Neoplasmer, Plasmacell
Andra studie-ID-nummer
- 209393
- ADP 01411 (Annan identifierare: Adaptimmune Therapeutics)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
IPD-planbeskrivning
Tidsram för IPD-delning
Kriterier för IPD Sharing Access
IPD-delning som stöder informationstyp
- STUDY_PROTOCOL
- SAV
- ICF
- CSR
Läkemedels- och apparatinformation, studiedokument
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