TCR Genetically Engineered PBMC and PBSC After Melphalan Conditioning Regimen in Treating Participants With Relapsed and Refractory Multiple Myeloma (NYSCT MM)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03506802|
Recruitment Status : Recruiting
First Posted : April 24, 2018
Last Update Posted : January 8, 2019
|Condition or disease||Intervention/treatment||Phase|
|HLA-A*0201 Positive Cells Present NY-ESO-1 Positive Tumor Cells Present Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma||Radiation: 18F-FHBG Biological: Aldesleukin Biological: Cellular Therapy Procedure: Computed Tomography Biological: Filgrastim Other: Laboratory Biomarker Analysis Drug: Lenalidomide Procedure: Leukapheresis Drug: Melphalan Drug: Plerixafor Procedure: Positron Emission Tomography||Phase 1|
I. To determine the safety of administering the combination of autologous peripheral blood mononuclear cells (PBMC) and CD34+ peripheral blood stem cells (PBSC) following a melphalan conditioning regimen, both of which have been genetically modified to express NY-ESO-1 TCR.
I. To determine the feasibility of delivering the combination of T-cell receptor (TCR) transduced autologous PBMC and CD34+ PBSC to patients.
II. To determine the persistence of NY-ESO-1 TCR transduced PBMC and the progeny of TCR transduced PBSC in serial peripheral blood samples.
III. Objective response rate (ORR).
I. To explore the use of positron emission tomography (PET)-based imaging using the PET tracer 9-4-[18F]fluoro-3-(hydroxymethyl)butylguanine ([18F]FHBG) with the goal of determining whether the adoptively transferred NY-ESO-1 TCR transduced PBSC home to bone marrow, differentiate into T cells and expand in secondary lymphoid organs and extramedullary disease sites.
G-CSF AND PLERIXAFOR MOBILIZED LEUKAPHERESIS: Between 6 months and 3 weeks before infusion of cells, participants undergo G-CSF and plerixafor mobilization of CD34+ peripheral blood stem cells. Participants receive filgrastim subcutaneously (SC) on mobilization days 1-4 and up to mobilization day 8 and plerixafor SC starting on mobilization day 4 up to day 8. During mobilization, participants will undergo mobilized leukapheresis to obtain PBSC. Participants also undergo an unmobilized leukapheresis on day -5 before infusion of cells in order to obtain PBMC.
CHEMOTHERAPY CONDITIONING REGIMEN: Participants receive melphalan intravenously (IV) on days -3 to -2.
Participants receive LV-NYESO TCR/sr39TK PBSC IV on day 0, and RV-NYESO TCR PBMC IV on day 1. Beginning on day 2, participants receive aldesleukin (interleukin-2 or IL-2) SC twice daily (BID) for up to 7 days. Participants receive the 18F-FHBG IV, and after 1 hour, undergo PET/computed tomography (CT) on days 30 and 90. After day 100, participants receive lenalidomide orally (PO) once daily (QD) for 21 days. Courses of lenalidomide repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up monthly after day 90 until disease progression and annually for up to 15 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Adoptive Transfer of NY-ESO-1 TCR Engineered Peripheral Blood Mononuclear Cells (PBMC) and Peripheral Blood Stem Cells (PBSC) After a High Dose Melphalan Conditioning Regimen, With Administration of Interleukin-2, in Patients With Multiple Myeloma|
|Actual Study Start Date :||July 10, 2018|
|Estimated Primary Completion Date :||May 2, 2021|
|Estimated Study Completion Date :||May 2, 2022|
Experimental: Treatment (Genetically engineered PBMC and PBSC)
Refer to outline
Other Name: Reporter Probe 18F-FHBG
Biological: Cellular Therapy
LV-NYESO TCR /sr39TK PBSC and RV-NYESO TCR PBMC given IV
Other Name: Cell Therapy
Procedure: Computed Tomography
Other: Laboratory Biomarker Analysis
Procedure: Positron Emission Tomography
- Incidence of dose limiting toxicity [ Time Frame: Up to 90 days ]Safety will be assessed by monitoring and recording potential adverse effects of the treatment using the Common Toxicity Criteria at each study visit. Subjects will be monitored by medical histories, physical examinations and blood studies to detect potential toxicities from the treatment. If there are no dose limiting toxicities observed, the cohort will be expanded to 12 subjects. If 1/3 are observed, up to 6 subjects will be recruited. If less than 2/6 are observed, the cohort will be expanded to a total of 12 subjects. If a dose limiting toxicity is observed in 2 or more of 6 subjects, then this dose level will have exceeded the 33% rate, and the study will be terminated.
- Feasibility of NY-ESO-1 TCR transgenic cells [ Time Frame: Up to 1 month after transgenic cell adoptive transfer ]The feasibility of manufacturing will be assessed as the number of manufacturing products meeting the lot release criteria after an acceptable number of CD34+ cells have been obtained.
- Persistence of transduced T cells [ Time Frame: Up to 2 years after transgenic cell adoptive transfer ]Analysis will be performed using immune monitoring techniques. The number of days until the percentage of cells expressing both NYESO-1 TCR and CD3 drops below the baseline percentage.
- Engraftment and persistence of transduced progeny T cells [ Time Frame: Up to 2 years after transgenic cell adoptive transfer ]Analysis will be performed using immune monitoring techniques. The number of days until the vector copy number in the progeny T cells is undetectable.
- Engraftment and persistence of transduced T cells and progeny T cells [ Time Frame: Up to 2 years after transgenic cell adoptive transfer ]Analysis will be performed both using immune monitoring and molecular techniques. The number of days until the vector copy number in the T cells is undetectable.
- Persistence of TCR gene transduced cells [ Time Frame: Up to 15 years ]Will be assessed by semi quantitative deoxyribonucleic acid-polymerase chain reaction using primers specific for vector sequence.
- Long term monitoring for replication competence of retrovirus (RCR) and lentivirus (RCL) [ Time Frame: Up to 12 months post cell administration ]Will be assessed by polymerase chain reaction.
- Immunological monitoring [ Time Frame: Up to 15 years ]Will be assessed by NY-ESO-1126-157/MHC dextramer analysis. Functional assays like enzyme-linked immunosorbent assay, intracellular cytokine staining, and/or multicytokine array assays will complement the results. Immunological assays will be compared between 1) pre-infusion peripheral blood mononuclear cells and peripheral blood stem cells, 2) an aliquot of the engineered peripheral blood lymphocytes and stem cells at the time of infusion and 3) cells recovered from patients? peripheral blood after adoptive transfer.
- Objective response [ Time Frame: Up to 15 years ]Potential objective responses to this combinatorial immunotherapy will be recorded following International Myeloma Working Group (IMWG) Response Criteria.
- Duration of overall complete response [ Time Frame: From the time measurement criteria has been first met for complete response until the first date that recurrent or progressive disease is objectively documented, assessed up to 15 years ]Will evaluate duration of overall complete response.
- Duration of overall response [ Time Frame: From the time measurement criteria is met for complete response/partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 15 years ]Will evaluate duration of overall response.
- Time to disease progression [ Time Frame: Time from the date of cell infusion (day 0) to the date of progressive disease first documented, or death whichever occurs first, assessed up to 15 years ]Will evaluate length of time until disease progression.
- LV-NYESO TCR/sr39TK peripheral blood stem cell (PBSC) biodistribution (Regional uptake of 18F-FHBG within metastatic tumor sites and secondary lymphoid organs) [ Time Frame: Day 30 and day 90 ]Will be quantified by standardized uptake values normalized to the body weight of the patient. As an internal quality control, standardized uptake values will also be determined for several normal organs, such as muscle, liver and lungs. These measurements will allow us to identify technical problems in the standardized uptake value calculations, such as partially paravenous tracer administration. Findings from non-invasive positron emission tomography imaging will be compared with results from immune monitoring assays in blood samples at different intervals after NY-ESO-1 TCR cell transplant.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03506802
|Contact: Paula Cabrera||310 206-2090||ISTWAM@mednet.ucla.edu|
|United States, California|
|UCLA / Jonsson Comprehensive Cancer Center||Recruiting|
|Los Angeles, California, United States, 90095|
|Contact: Paula Cabrea 310-206-2090 ISTWAM@mednet.ucla.edu|
|Principal Investigator: Sarah Larson, M.D.|
|Principal Investigator:||Sarah Larson, M.D.||UCLA / Jonsson Comprehensive Cancer Center|