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Redirected Auto T Cells for Advanced Myeloma

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ClinicalTrials.gov Identifier: NCT01352286
Recruitment Status : Completed
First Posted : May 11, 2011
Results First Posted : January 3, 2019
Last Update Posted : December 3, 2019
Information provided by (Responsible Party):

Tracking Information
First Submitted Date  ICMJE May 4, 2011
First Posted Date  ICMJE May 11, 2011
Results First Submitted Date  ICMJE July 10, 2018
Results First Posted Date  ICMJE January 3, 2019
Last Update Posted Date December 3, 2019
Actual Study Start Date  ICMJE May 13, 2011
Actual Primary Completion Date August 25, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 8, 2018)
Adverse Events Related to Study Treatment [ Time Frame: Day -40 to Year 1 post-treatment ]
Number of Participants with Adverse Events related to study treatment
Original Primary Outcome Measures  ICMJE
 (submitted: May 10, 2011)
Study related adverse events
Monitoring for occurrences of study related adverse events
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2018)
  • 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 ]
    Objective Response Rate (ORR) of sCR (stringent complete response), CR (complete response), VGPR (very good partial response), PR (partial response)
  • Best Objective Response (BOR) [ Time Frame: Best Objective Response prior to initiation of lenalidomide and at Year 1 ]
    Number of participants with Best Objective Response of sCR, CR, VGPR, or PR
  • 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. ]
    Calculated median DOR, PFS, OS
  • Peak Persistence of Modified T-cells in the Peripheral Blood [ Time Frame: Post-infusion through Day 42 ]
    Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood
  • Marrow Antigen Expression Pre-and Post-infusion [ Time Frame: Pre- and post-infusion ]
    Number of participants with NY-ESO-1 and LAGE or LAGE-1a expression in the marrow post-infusion
  • Engraftment of Gene-modified Pentamer+ CD4+ T Cells and CD8+ T Cells [ Time Frame: Post Treatment ]
    Number of participants with engraftment in blood and bone marrow
Original Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2011)
Clinical Response Rate [ Time Frame: at day 180 ]
Measuring Clinical Response Rate to treatment.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Redirected Auto T Cells for Advanced Myeloma
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE Genetic: Autologous Genetically modified T cells

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.

Study Arms  ICMJE Experimental: 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.
Intervention: Genetic: Autologous Genetically modified T cells
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 8, 2018)
Original Estimated Enrollment  ICMJE
 (submitted: May 10, 2011)
Actual Study Completion Date  ICMJE July 8, 2019
Actual Primary Completion Date August 25, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01352286
Other Study ID Numbers  ICMJE 209393
ADP 01411 ( Other Identifier: Adaptimmune Therapeutics )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: https://clinicalstudydatarequest.com/Posting.aspx?ID=20063
Current Responsible Party GlaxoSmithKline
Original Responsible Party Ed Stadtmauer, MD, Principal Investigator, Abramson Cancer Center of the University of Pennsylvania
Current Study Sponsor  ICMJE GlaxoSmithKline
Original Study Sponsor  ICMJE Abramson Cancer Center of the University of Pennsylvania
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP