Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Autologous stem cell transplantation, Received initial treatment previously
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.
Interventions
DRUGTreatment 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.
Sponsors
Adaptimmune
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events Related to Study Treatment | Up to 12 months | Number of Participants with NCI CTCAE Version 4.0 Adverse Events related to study treatment greater than or equal to Grade 3 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Direct Anti-tumor Activity of NY-ESO-1ᶜ²⁵⁹T | 180 days | Number of participants with response post-infusion as assessed by international uniform response criteria |
| Peak Persistence of Modified T-cells in the Peripheral Blood | Days 1, 3, 5, 8, 15, 22, 29, 43, 101, 130 181, every 3 months thereafter | Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood (copies of WPRE per µg of genomic PBMC DNA) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NY-ESO-1ᶜ²⁵⁹T Cells Administered IV Participants who received cytoreductive chemotherapy followed by infusion of lentivirus-mediated genetically engineered NY-ESO-1ᶜ²⁵⁹T (Target dose: 1-10 billion cells) | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Apheresed but not treated | 4 |
Baseline characteristics
| Characteristic | NY-ESO-1ᶜ²⁵⁹T Cells Administered IV |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 64.5 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 2 |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 1 / 2 |
Outcome results
Primary
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
Time frame: Up to 12 months
Population: Participants who received NY-ESO-1ᶜ²⁵⁹T
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NY-ESO-1ᶜ²⁵⁹T Cells Administered IV | Adverse Events Related to Study Treatment | 2 Participants |
Secondary
Evaluate the Direct Anti-tumor Activity of NY-ESO-1ᶜ²⁵⁹T
Number of participants with response post-infusion as assessed by international uniform response criteria
Time frame: 180 days
Population: Participants who received NY-ESO-1ᶜ²⁵⁹T
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NY-ESO-1ᶜ²⁵⁹T Cells Administered IV | Evaluate the Direct Anti-tumor Activity of NY-ESO-1ᶜ²⁵⁹T | 0 Participants |
Secondary
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)
Time frame: Days 1, 3, 5, 8, 15, 22, 29, 43, 101, 130 181, every 3 months thereafter
Population: Participants who received cytoreductive chemotherapy followed by infusion of NY-ESO-1ᶜ²⁵⁹T with persistence data
| Arm | Measure | Value (MEAN) |
|---|---|---|
| NY-ESO-1ᶜ²⁵⁹T Cells Administered IV | Peak Persistence of Modified T-cells in the Peripheral Blood | 29,179 copies per μg of DNA |