Redirected Auto T Cells for Advanced Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Autologous Genetically modified T cells
Intervention 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Multiple myeloma; Received initial treatment previously; Autologous stem cell transplantation

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.
    

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