CT Antigen TCR-Engineered T Cells for Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Adaptimmune
ClinicalTrials.gov Identifier:
NCT01892293
First received: June 27, 2013
Last updated: June 9, 2016
Last verified: June 2016
  Purpose
This study will enroll patients with multiple myeloma who have received prior therapy for their disease but their disease has progressed or relapsed.

Condition Intervention Phase
Multiple Myeloma
Drug: Treatment with NY-ESO-1c259-modified T cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Adaptimmune:

Primary Outcome Measures:
  • Safety and Tolerability [ Time Frame: 3 Years ] [ Designated as safety issue: Yes ]
    Statistical analysis for this study will be primarily descriptive. The evaluable population includes any patient who has received the T cell infusion at the target dose range of ≥1e9-1e10 NY-ESO-1c259-T. For the primary safety endpoints, all adverse events will be described and exact 95% confidence intervals will be produced for adverse event rates, both overall and within major categories.


Secondary Outcome Measures:
  • Evaluate the direct anti-tumor activity of NY-ESO-1c259-T [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
    Analysis of secondary endpoints (e.g., response rate) will be descriptive and may include summary statistics such as means, median, standard deviations, range, and proportions. Confidence intervals will be computed. Endpoints that are taken repeatedly over time will be summarized and plotted against time since infusion to identify patterns over time.


Estimated Enrollment: 10
Study Start Date: September 2013
Estimated Study Completion Date: April 2031
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Autologous genetically modified T cells
Patients 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.
Drug: 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.

For patients whose disease progresses and whose tumor still expresses tumor antigen and HLA-A201, a second infusion of up to 5e10 cells may be given.


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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

    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 therapy
    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 antigen.
    • 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01892293

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
United States, Maryland
Greenebaum Cancer Center, University of Maryland
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
Adaptimmune
Investigators
Study Chair: Aaron Rapoport, MD University of Maryland
  More Information

Responsible Party: Adaptimmune
ClinicalTrials.gov Identifier: NCT01892293     History of Changes
Other Study ID Numbers: ADP-0011-002 
Study First Received: June 27, 2013
Last Updated: June 9, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Adaptimmune:
Multiple Myeloma
Autologous stem cell transplantation
Received initial treatment previously

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 26, 2016