Ignite Creation Date:
2025-12-25 @ 3:45 AM
Ignite Modification Date:
2025-12-26 @ 2:32 AM
Study NCT ID:
NCT03506802
Status:
WITHDRAWN
Last Update Posted:
2020-07-24
First Post:
2018-04-13
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
TCR Genetically Engineered PBMC and PBSC After Melphalan Conditioning Regimen in Treating Participants With Relapsed and Refractory Multiple Myeloma
Sponsor:
Jonsson Comprehensive Cancer Center
Organization:
Study Overview
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
Status:
WITHDRAWN
Status Verified Date:
2019-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
No Participants Enrolled
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NYSCT MM
Brief Summary:
This phase I trial studies the side effects of NY-ESO-1 TCR engineered peripheral blood mononuclear cells (PBMC) and peripheral blood stem cells (PBSC) after melphalan conditioning regimen in treating participants with multiple myeloma that has come back or does not respond to treatment. The melphalan conditioning chemotherapy makes room in the patient?s bone marrow for new blood cells (PBMC) and blood-forming cells (stem cells) to grow. Giving NY-ESO-1 TCR PBMC and stem cells after the conditioning chemotherapy is intended to replace the immune system with new immune cells that have been redirected to attack and kill the cancer cells and thereby improve immune system function against cancer. Giving NY-ESO-1 TCR PBMC and PBSC after melphalan may work better at treating multiple myeloma.
Detailed Description:
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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).
TERTIARY OBJECTIVES:
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.
OUTLINE:
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.
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.
SECONDARY OBJECTIVES:
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).
TERTIARY OBJECTIVES:
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.
OUTLINE:
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: