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CT Antigen TCR-Engineered T Cells for Myeloma

Primary Purpose

Multiple Myeloma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

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

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Autologous stem cell transplantation, Received initial treatment previously

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

City of Hope
Greenebaum Cancer Center, University of Maryland

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Autologous genetically modified T cells

Arm Description

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.

Outcomes

Primary Outcome Measures

Adverse Events Related to Study Treatment

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

Evaluate the Direct Anti-tumor Activity of NY-ESO-1ᶜ²⁵⁹T

Number of participants with response post-infusion as assessed by international uniform response criteria

Peak Persistence of Modified T-cells in the Peripheral Blood

Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood (copies of WPRE per µg of genomic PBMC DNA)

Full Information

NCT ID

NCT01892293

First Posted

June 27, 2013

Last Updated

January 8, 2019

Sponsor

Adaptimmune

1. Study Identification

Unique Protocol Identification Number

NCT01892293

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Terminated

Why Stopped

Sponsor Decision

Study Start Date

October 15, 2013 (Actual)

Primary Completion Date

December 10, 2014 (Actual)

Study Completion Date

April 9, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Adaptimmune

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Autologous genetically modified T cells

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

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

Intervention Description

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.

Primary Outcome Measure Information:

Title

Adverse Events Related to Study Treatment

Description

Number of Participants with NCI CTCAE Version 4.0 Adverse Events related to study treatment greater than or equal to Grade 3

Time Frame

Up to 12 months

Secondary Outcome Measure Information:

Title

Evaluate the Direct Anti-tumor Activity of NY-ESO-1ᶜ²⁵⁹T

Description

Number of participants with response post-infusion as assessed by international uniform response criteria

Time Frame

180 days

Title

Peak Persistence of Modified T-cells in the Peripheral Blood

Description

Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood (copies of WPRE per µg of genomic PBMC DNA)

Time Frame

Days 1, 3, 5, 8, 15, 22, 29, 43, 101, 130 181, every 3 months thereafter

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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: includes an IMiD and proteasome inhibitor as separate lines or a combined line of therapy 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Edward Stadtmauer, MD

Organizational Affiliation

University of Pennsylvania

Official's Role

Study Chair

Facility Information:

Facility Name

City of Hope

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

Facility Name

Greenebaum Cancer Center, University of Maryland

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

12. IPD Sharing Statement

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CT Antigen TCR-Engineered T Cells for Myeloma

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