Clinical Trials /

CT Antigen TCR-Engineered T Cells for Myeloma



This study will enroll patients with multiple myeloma who have received prior therapy for their disease but their disease has progressed or relapsed.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:



Phase 1/Phase 2

Trial Eligibility



  • Brief Title: CT Antigen TCR-Engineered T Cells for Myeloma
  • Official Title: A Phase I/IIa, Open Label, Multiple Site Clinical Trial Evaluating the Safety and Activity of Engineered Autologous T Cells Expressing an Affinity-enhanced TCR Specific for NY-ESO-1 and LAGE-1 in Patients With Relapsed or Progressive Disease in Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: ADP-0011-002
  • NCT ID: NCT01892293


  • Multiple Myeloma


Treatment with NY-ESO-1c259-modified T cellsAutologous genetically modified T cells


This study will enroll patients with multiple myeloma who have received prior therapy for their disease but their disease has progressed or relapsed.

Detailed Description

      The primary objective of the study is to evaluate the safety and tolerability of autologous
      genetically modified T cells transduced to express the high affinity NY-ESO-1c259 TCR in
      HLA-A201 patients. Eligibility screening will be performed in two steps. First, patients will
      undergo prescreening to determine if they have the correct HLA type in order to respond to
      the engineered T cell therapy, and to test for presence of the target antigen, NY-ESO-1 and
      LAGE-1, in their tumor cells. Patients, who are HLA-A201 positive and test positive for
      expression of NY-ESO-1 and/or LAGE-1 in their myeloma tumor will move on to complete all
      screening procedures to determine eligibility for the study.

      Patients will initially undergo a steady-state mononuclear cell apheresis for T cell
      collection. About 3-4 weeks later (to allow expansion/engineering/releasing the engineered T
      cells), patients will receive a short course of cytoreductive chemotherapy prior to receiving
      the engineered T cell infusion, comprised of 1.5 gm/m2 of cyclophosphamide, mesna will be
      given if in accordance with institutional standards.

      At day 0, patients will receive a dose of ≥0.1-1 x 1010 anti-CD3/anti-CD28-costimulated
      autologous T cells which have been genetically modified to express affinity-enhanced NY-ESO-1
      T cell receptors (TCRs). A minimum dose of 0.1≤x<1 x 109 will be permitted. Patients
      receiving this low dose level will be evaluated separately for safety and efficacy.

      Patients will undergo myeloma restaging approximately 1 week prior to the T cell infusion,
      and post infusion at days +28, +42 (week 6), +100 and 6 months post infusion and then every 3
      months until relapse/progression or until 1 year, whenever comes first. At this point,
      patients will be followed semi-annually for up to 5 years and then annually for long term
      follow-up for monitoring for delayed adverse events until 15 years after receiving the
      genetically modified T cells, in accordance with FDA Guidelines.

Trial Arms

Autologous genetically modified T cellsExperimentalPatients with a confirmed diagnosis of myeloma, with measurable disease, and who have received prior therapy for their myeloma that includes an IMiDs and a proteasome inhibitor and who have relapsed or progressive disease, will receive treatment with NY-ESO-1c259-modified T cells. An intended total dose of ≥0.1-1e10 total cells will be administered as a single infusion. A low dose infusion of 1e8 to < 1e9 will be allowed for patients if cells do not expand sufficiently to reach the target dose range.
  • Treatment with NY-ESO-1c259-modified T cells

Eligibility Criteria

        Inclusion Criteria:

          -  1. Written informed consent must be obtained from all patients before entry into the

             2. Patients must have a diagnosis of myeloma (see Appendix A for diagnostic criteria).

             3. Patients must have progressive or active disease following prior therapy for their
             myeloma which:

               1. includes an IMiD and proteasome inhibitor as separate lines or a combined line of

               2. May include prior auto-SCT but not prior allo-SCT

                  Patients who have failed second or third line therapy and beyond, such as DPACE,
                  and who are experiencing a partial response rather than progressive disease are
                  also eligible.

                  4. Patients 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 on study entry, serum free kappa or
                  lambda light chain levels, or the serum free light chain ratio may be measured
                  and used for disease monitoring if abnormal.

                  5. Patients must be HLA-A201 as determined by a CLIA certified (or equivalent)
                  clinical laboratory. (This determination will be made under a pre-enrollment
                  screening ICF)

                  6. Patients must have confirmed expression of NY-ESO-1 and/or LAGE-1 by RT-PCR,
                  immunohistochemistry or quantigene analysis. (This determination will be made
                  under a pre-enrollment screening ICF)

                  Exclusion Criteria:

          -  1. Pregnant or nursing females 2. HIV or HTLV-1/2 seropositivity 3. Known history of
             myelodysplasia 4. Known history of chronic active hepatitis or liver cirrhosis (if
             suspected by laboratory studies, should be confirmed by liver biopsy).

             5. Active Infection with HBV or HCV

               -  Active hepatitis B infection as determined by test for hepatitis B surface

               -  Active hepatitis C. Patients will be screened for HCV antibody. If the HCV
                  antibody is positive, a screening HCV RNA by any RT PCR or bDNA assay must be
                  performed at screening by a local laboratory with a CLIA certification or its
                  equivalent. Eligibility will be determined based on a negative screening value.
                  The test is not required if documentation of a negative result of a HCV RNA test
                  performed within 60 days prior to screening is provided.

                  6. Prior allogeneic transplant 7. History of severe autoimmune disease requiring
                  steroids or other immunosuppressive treatments.

                  8. Active immune-mediated diseases including: connective tissue diseases,
                  uveitis, sarcoidosis, inflammatory bowel disease, multiple sclerosis.

                  9. 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. The specific type of stress
                  test will be selected at the PI's discretion.

                  10. Active bacterial or systemic viral or fungal infections.
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events Related to Study Treatment
Time Frame:Up to 12 months
Safety Issue:
Description:Number of Participants with NCI CTCAE Version 4.0 Adverse Events related to study treatment greater than or equal to Grade 3

Secondary Outcome Measures

Measure:Evaluate the Direct Anti-tumor Activity of NY-ESO-1ᶜ²⁵⁹T
Time Frame:180 days
Safety Issue:
Description:Number of participants with response post-infusion as assessed by international uniform response criteria
Measure:Peak Persistence of Modified T-cells in the Peripheral Blood
Time Frame:Days 1, 3, 5, 8, 15, 22, 29, 43, 101, 130 181, every 3 months thereafter
Safety Issue:
Description:Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood (copies of WPRE per µg of genomic PBMC DNA)


Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Adaptimmune

Trial Keywords

  • Multiple Myeloma
  • Autologous stem cell transplantation
  • Received initial treatment previously

Last Updated

January 10, 2019