Ignite Creation Date:
2024-05-06 @ 1:12 PM
Last Modification Date:
2024-10-26 @ 1:10 PM
Study NCT ID:
NCT03958656
Status:
COMPLETED
Last Update Posted:
2021-09-09
First Post:
2019-05-21
Brief Title:
T-cells Expressing an Anti-SLAMF7 CAR for Treating Multiple Myeloma
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase I Clinical Trial of T-cells Expressing an Anti-SLAMF7 CAR for Treating Multiple Myeloma
Status:
COMPLETED
Status Verified Date:
2021-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Multiple myeloma is a blood cancer that is usually incurable T cells are part of the immune system Researchers think changing a persons T cells to recognize their cancer could help the persons body kill tumor cells This is a new approach that uses a patients own cells to target multiple myeloma
Objective
To see if giving anti-Signaling lymphocytic activation molecule F7 SLAM7 chimeric antigen receptor CAR T cells with a stop switch to people with multiple myeloma is safe and to see if adding a gene to stop T-cell activity can limit toxicity of this therapy
Eligibility
People ages 18-73 with multiple myeloma for which prior standard treatment has not worked
Design
Participants will be screened with
Medical history
Physical exam
Blood urine and heart tests
Bone marrow samples A needle inserted into the participants bone will remove marrow
Imaging scans Participants will lie in a machine that takes pictures of the body
Participants will have apheresis They will receive a catheter or central line A plastic tube will be inserted into a chest or arm vein Blood will be removed and the T cells separated The rest of the blood will be returned to the participant The T cells will be manipulated in the lab
Participants will get chemotherapy through the central line for 3 days
Participants will receive the manipulated T cells through the central line They will stay in the hospital at least 9 days
Participants will have follow-up visits 2 weeks then 1 2 3 4 6 9 and 12 months after the infusion They will then have visits every 6 months for 3 years Then they will be contacted once per year for 15 years All visits will include blood tests and 3 visits will include bone marrow biopsies
Multiple myeloma is a blood cancer that is usually incurable T cells are part of the immune system Researchers think changing a persons T cells to recognize their cancer could help the persons body kill tumor cells This is a new approach that uses a patients own cells to target multiple myeloma
Objective
To see if giving anti-Signaling lymphocytic activation molecule F7 SLAM7 chimeric antigen receptor CAR T cells with a stop switch to people with multiple myeloma is safe and to see if adding a gene to stop T-cell activity can limit toxicity of this therapy
Eligibility
People ages 18-73 with multiple myeloma for which prior standard treatment has not worked
Design
Participants will be screened with
Medical history
Physical exam
Blood urine and heart tests
Bone marrow samples A needle inserted into the participants bone will remove marrow
Imaging scans Participants will lie in a machine that takes pictures of the body
Participants will have apheresis They will receive a catheter or central line A plastic tube will be inserted into a chest or arm vein Blood will be removed and the T cells separated The rest of the blood will be returned to the participant The T cells will be manipulated in the lab
Participants will get chemotherapy through the central line for 3 days
Participants will receive the manipulated T cells through the central line They will stay in the hospital at least 9 days
Participants will have follow-up visits 2 weeks then 1 2 3 4 6 9 and 12 months after the infusion They will then have visits every 6 months for 3 years Then they will be contacted once per year for 15 years All visits will include blood tests and 3 visits will include bone marrow biopsies
Detailed Description:
Background
Multiple myeloma MM is a nearly always incurable malignancy of plasma cells
T cells can be genetically modified to express chimeric antigen receptors CARs that target malignancy-associated antigens
Signaling lymphocytic activation molecule F7 SLAM7 is highly and uniformly expressed on MM cells but is absent on normal tissues except for some leukocytes including a subset of cluster of differentiation 8 CD8 T cells natural killer NK cells B cells plasma cells and monocytes
We have constructed a novel anti-SLAMF7 CAR that can specifically recognize SLAMF7- expressing target cells and eradicate SLAMF7-expressing tumors in mice
This protocol will test genetic modification of autologous T cells with genes encoding an inducible caspase 9 IC9 cell-suicide system plus the anti-SLAMF7 CAR
Administration of the dimerizer drug Rimiducid AP1903 is necessary to activate the inducible caspase 9 IC9 suicide gene and eliminate CAR T cells
In this protocol the suicide gene system will be used to eliminate CAR-expressing T cells in case of severe toxicities caused by the CAR T cells
Possible toxicities include cytokine-associated toxicities such as hypotension and neurological toxicities Elimination of NK cells and normal plasma cells could make patients more susceptible to infections Unknown toxicities are also possible
Objectives
Primary
- Determine the safety feasibility of administering T cells expressing an anti-SLAMF7 CAR plus IC9 cell-suicide system to patients with MM
Eligibility
Greater than or equal to 18 years of age and less than or equal to age 73
Patients must have measurable MM defined as a serum M-protein 06 gdL or a urine M-protein 200 mg24 hours or an involved serum free light chain FLC level 10 mgdL provided FLC ratio is abnormal or a biopsy-proven plasmacytoma of 15 cm or more in largest dimension or greater than or equal to 30 bone marrow plasma cells
Patients must have previously received at least 3 different treatment regimens for MM
Patients must have prior exposure to an immunomodulatory drug IMiD such as lenalidomide and a proteasome inhibitor
Patients must have a creatinine level of less than or equal to 15 mgdL
Patients must have a cardiac ejection fraction 50
An Eastern Cooperative Oncology Group ECOG performance status of 0-2 is required
Patients on any anticoagulant medications except aspirin are not eligible
No active infections are allowed
Absolute neutrophil count 1000microL platelet count 55000microL hemoglobin 8gdL
Alanine aminotransferase ALT and aspartate aminotransferase AST less than or equal to 25-fold higher than the upper limit of normal
At least 14 days must elapse between the time of any prior systemic treatment including corticosteroids and the required leukapheresis
At least 14 days must elapse between the time of any prior systemic treatment and initiation of protocol treatment Systemic therapy includes corticosteroids at a dose equivalent to more than 5 mg of prednisone
Bone marrow plasma cells must make up less than or equal to 50 of total bone marrow cells less than or equal to 24 days prior to the start of protocol treatment
The patients MM will need to be assessed for SLAMF7 expression by flow cytometry or immunohistochemistry performed at the National Institutes of Health NIH The myeloma must express SLAMF7 If unstained paraffin-embedded bone marrow or plasmacytoma sections are available from prior biopsies these can be used to determine SLAMF7 expression by immunohistochemistry otherwise patients will need to come to the NIH for a bone marrow biopsy or other biopsy of a plasmacytoma to determine SLAMF7 expression The sample for SLAMF7 expression can come from a biopsy obtained at any time before enrollment
Design
This is a phase I dose-escalation trial
Patients will undergo leukapheresis and T cells will be modified to express the IC9-anti-SLAMF7 CAR construct
The chemotherapy conditioning regimen is cyclophosphamide 300 mgm2 daily for 3 days and fludarabine 30 mgm2 daily for 3 days The intent of chemotherapy is to enhance CAR T-cell activity
After the chemotherapy ends the patients will have two days with no treatments and then receive an infusion of CAR T cells
The initial dose level will be 066x106 Anti-SLAMF7-CAR T cellskg of recipient bodyweight
The cell dose administered will be escalated for up to 4 doses until a maximum tolerated dose is determined
Following the T-cell infusion there will be a mandatory 9-day minimum inpatient hospitalization to monitor for toxicity
Outpatient follow-up is planned for 2 weeks and 1 2 3 4 6 9 and 12 months after the CAR T-cell infusion Afterwards follow-up will be every six months up to at least 3 years after infusion
Multiple myeloma MM is a nearly always incurable malignancy of plasma cells
T cells can be genetically modified to express chimeric antigen receptors CARs that target malignancy-associated antigens
Signaling lymphocytic activation molecule F7 SLAM7 is highly and uniformly expressed on MM cells but is absent on normal tissues except for some leukocytes including a subset of cluster of differentiation 8 CD8 T cells natural killer NK cells B cells plasma cells and monocytes
We have constructed a novel anti-SLAMF7 CAR that can specifically recognize SLAMF7- expressing target cells and eradicate SLAMF7-expressing tumors in mice
This protocol will test genetic modification of autologous T cells with genes encoding an inducible caspase 9 IC9 cell-suicide system plus the anti-SLAMF7 CAR
Administration of the dimerizer drug Rimiducid AP1903 is necessary to activate the inducible caspase 9 IC9 suicide gene and eliminate CAR T cells
In this protocol the suicide gene system will be used to eliminate CAR-expressing T cells in case of severe toxicities caused by the CAR T cells
Possible toxicities include cytokine-associated toxicities such as hypotension and neurological toxicities Elimination of NK cells and normal plasma cells could make patients more susceptible to infections Unknown toxicities are also possible
Objectives
Primary
- Determine the safety feasibility of administering T cells expressing an anti-SLAMF7 CAR plus IC9 cell-suicide system to patients with MM
Eligibility
Greater than or equal to 18 years of age and less than or equal to age 73
Patients must have measurable MM defined as a serum M-protein 06 gdL or a urine M-protein 200 mg24 hours or an involved serum free light chain FLC level 10 mgdL provided FLC ratio is abnormal or a biopsy-proven plasmacytoma of 15 cm or more in largest dimension or greater than or equal to 30 bone marrow plasma cells
Patients must have previously received at least 3 different treatment regimens for MM
Patients must have prior exposure to an immunomodulatory drug IMiD such as lenalidomide and a proteasome inhibitor
Patients must have a creatinine level of less than or equal to 15 mgdL
Patients must have a cardiac ejection fraction 50
An Eastern Cooperative Oncology Group ECOG performance status of 0-2 is required
Patients on any anticoagulant medications except aspirin are not eligible
No active infections are allowed
Absolute neutrophil count 1000microL platelet count 55000microL hemoglobin 8gdL
Alanine aminotransferase ALT and aspartate aminotransferase AST less than or equal to 25-fold higher than the upper limit of normal
At least 14 days must elapse between the time of any prior systemic treatment including corticosteroids and the required leukapheresis
At least 14 days must elapse between the time of any prior systemic treatment and initiation of protocol treatment Systemic therapy includes corticosteroids at a dose equivalent to more than 5 mg of prednisone
Bone marrow plasma cells must make up less than or equal to 50 of total bone marrow cells less than or equal to 24 days prior to the start of protocol treatment
The patients MM will need to be assessed for SLAMF7 expression by flow cytometry or immunohistochemistry performed at the National Institutes of Health NIH The myeloma must express SLAMF7 If unstained paraffin-embedded bone marrow or plasmacytoma sections are available from prior biopsies these can be used to determine SLAMF7 expression by immunohistochemistry otherwise patients will need to come to the NIH for a bone marrow biopsy or other biopsy of a plasmacytoma to determine SLAMF7 expression The sample for SLAMF7 expression can come from a biopsy obtained at any time before enrollment
Design
This is a phase I dose-escalation trial
Patients will undergo leukapheresis and T cells will be modified to express the IC9-anti-SLAMF7 CAR construct
The chemotherapy conditioning regimen is cyclophosphamide 300 mgm2 daily for 3 days and fludarabine 30 mgm2 daily for 3 days The intent of chemotherapy is to enhance CAR T-cell activity
After the chemotherapy ends the patients will have two days with no treatments and then receive an infusion of CAR T cells
The initial dose level will be 066x106 Anti-SLAMF7-CAR T cellskg of recipient bodyweight
The cell dose administered will be escalated for up to 4 doses until a maximum tolerated dose is determined
Following the T-cell infusion there will be a mandatory 9-day minimum inpatient hospitalization to monitor for toxicity
Outpatient follow-up is planned for 2 weeks and 1 2 3 4 6 9 and 12 months after the CAR T-cell infusion Afterwards follow-up will be every six months up to at least 3 years after infusion
Study Oversight
Has Oversight DMC:
None
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?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 19-C-0102 | None | None | None |