Redirected Auto T Cells for Advanced Myeloma

The primary objective is to evaluate the safety and tolerability of autologous genetically modified T cells transduced to express the high affinity of MAGE-A3 TCR in HLA-A1 subjects and the high affinity NYESO-1 TCR in HLA-A2 subjects.

Purpose 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.

• Systemic Myeloma
• Multifocal Myeloma

• Genetic: Autologous Genetically modified T cells
• Biological: Prevnar -13

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).
• Failure to respond would correspond to a reduction of less than or equal to 25%of the original, diagnostic serum or urine paraprotein measurement.
• Myeloma has responded partially to initial therapy but a complete response (immunofixation negative and normal serum free light chain studies) 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 autotransplants: complex karyotype (greater or equal 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.

Extended disease-free survival after autotransplantation would be unexpected for these patients and therefore especially meaningful.

• Subjects must have measurable disease on study entry. Measurable disease may include quantifiable or detectable levels of serum or urine paraprotein. For patients with minimally secretory disease or non-secretory myeloma on study entry, serum free lamda or kappa light chain levels or the serum free light chain ratio may be measured and used for disease monitoring if abnormal.
• Subjects mus have ECOG score of 0-2 (unless due solely to bone pain)
• Female 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.
• 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. Lemalidomide 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-A1 patients must have confirmed MAGE-A3/6 expression on the marrow biopsy specimen and HLA-A2 patients must have confirmed expression of NY-ESO-1 (these determinations will be under a preenrollment screening consent form using criteria listed below in study procedures.)

Exclusion Criteria:

• Pregnant or nursing females
• HIV or HTLV - 1/2 seropositivity
• Known history of myelodysplasia
• Known 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.

• University of Maryland Greenebaum Cancer Center
• Adaptimmune