Ignite Creation Date:
2024-05-06 @ 8:50 AM
Last Modification Date:
2024-10-26 @ 12:05 PM
Study NCT ID:
NCT02830724
Status:
RECRUITING
Last Update Posted:
2024-07-01
First Post:
2016-07-12
Brief Title:
Administering Peripheral Blood Lymphocytes Transduced With a CD70-Binding Chimeric Antigen Receptor to People With CD70 Expressing Cancers
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase III Study Administering Peripheral Blood Lymphocytes Transduced With a CD70-Binding Chimeric Antigen Receptor to Patients With CD70-Expressing Cancers
Status:
RECRUITING
Status Verified Date:
2024-09-26
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
In a new cancer therapy researchers take a person s blood select a certain white blood cell to grow in the lab and then change the genes of these cells using a virus The cells are then given back to the person This is called gene transfer For this study researchers will modify the person s white blood cells with anti-CD70
Objectives
To see if a gene transfer with anti-CD70 cells can safely shrink tumors and to be certain the treatment is safe
Eligibility
Adults age 18 and older diagnosed with cancer that has the CD70-expressing cancer
Design
Participants will be screened with medical history physical exam scans and other tests They may by admitted to the hospital Leukapheresis will be performed For this blood is removed through a needle in the arm A machine separates the white blood cells The rest of the blood is returned through a needle in the other arm
Eligible participants will have an intravenous catheter placed in their upper chest Over several days they will get chemotherapy drugs and the anti-CD70 cells They will recover in the hospital
Participants will take an antibiotic for 6 months after treatment They will repeat leukapheresis
Participants will visit the clinic every 1-3 months for the first year after treatment every 6 months for the second year and then as determined by their physician Follow-up visits will take 1-2 days At each visit participants will have lab tests imaging studies and a physical exam
Throughout the study blood will be taken and participants will have many tests to determine the size and extent of their tumor and the treatment s impact
In a new cancer therapy researchers take a person s blood select a certain white blood cell to grow in the lab and then change the genes of these cells using a virus The cells are then given back to the person This is called gene transfer For this study researchers will modify the person s white blood cells with anti-CD70
Objectives
To see if a gene transfer with anti-CD70 cells can safely shrink tumors and to be certain the treatment is safe
Eligibility
Adults age 18 and older diagnosed with cancer that has the CD70-expressing cancer
Design
Participants will be screened with medical history physical exam scans and other tests They may by admitted to the hospital Leukapheresis will be performed For this blood is removed through a needle in the arm A machine separates the white blood cells The rest of the blood is returned through a needle in the other arm
Eligible participants will have an intravenous catheter placed in their upper chest Over several days they will get chemotherapy drugs and the anti-CD70 cells They will recover in the hospital
Participants will take an antibiotic for 6 months after treatment They will repeat leukapheresis
Participants will visit the clinic every 1-3 months for the first year after treatment every 6 months for the second year and then as determined by their physician Follow-up visits will take 1-2 days At each visit participants will have lab tests imaging studies and a physical exam
Throughout the study blood will be taken and participants will have many tests to determine the size and extent of their tumor and the treatment s impact
Detailed Description:
Background
We generated a chimeric antigen receptor CAR that engages CD70 using its natural ligand CD27 as the binding moiety Transducing peripheral blood lymphocytes PBL with this CAR conveys major histocompatibility complex MHC-independent recognition of CD70-expressing target cells which include renal cell carcinoma and other cancers
In co-cultures with CD70 target cells anti-hCD70 CAR transduced T cells secrete significant amounts of IFN-gamma with high specificity
Objectives
Primary objectives
Phase I Determine the safety of administering PBL transduced with anti-hCD70 CAR in concert with preparative lymphodepletion and high dose interleukin-2 IL-2 aldesleukin
Phase II Determine if anti-hCD70 CAR-transduced PBL can mediate the regression of CD70 expressing tumors
Eligibility
Patients must behave
Age 18 years and 72 years
Metastatic or unresectable CD70-expressing cancer which has progressed after standard therapy
Patients may not have
Allergies or hypersensitivities to high-dose aldesleukin cyclophosphamide or fludarabine
Design
This is a phase III single center study of PBL transduced with anti-hCD70 CAR in patients with measurable unresectable cancer expressing CD70
PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 OKT3 and aldesleukin in order to stimulate T-cell growth
Transduction is initiated by exposure of these cells to retroviral vector supernatant containing replication-incompetent virus encoding the anti-hCD70 CAR
All patients will receive a non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine
On day 0 patients will receive PBL transduced with the anti-hCD70 CAR and will then begin high-dose aldesleukin
A complete evaluation of lesions will be conducted approximately 6 weeks plus or minus two weeks after treatment
The study will be conducted using a Phase III optimal design with two separate cohorts for the Phase II componentCohort 2a patients with CD70-expressing clear cell renal cell carcinoma RCC and Cohort 2b patients with a CD70-expressing non-RCC malignancy solid tumors only
A total of up to 124 patients may be required approximately 38 patients in the Phase I portion of the study and 43 41 plus an allowance of up to 2 non-evaluable patients in each cohort of the Phase II portion of the study
We generated a chimeric antigen receptor CAR that engages CD70 using its natural ligand CD27 as the binding moiety Transducing peripheral blood lymphocytes PBL with this CAR conveys major histocompatibility complex MHC-independent recognition of CD70-expressing target cells which include renal cell carcinoma and other cancers
In co-cultures with CD70 target cells anti-hCD70 CAR transduced T cells secrete significant amounts of IFN-gamma with high specificity
Objectives
Primary objectives
Phase I Determine the safety of administering PBL transduced with anti-hCD70 CAR in concert with preparative lymphodepletion and high dose interleukin-2 IL-2 aldesleukin
Phase II Determine if anti-hCD70 CAR-transduced PBL can mediate the regression of CD70 expressing tumors
Eligibility
Patients must behave
Age 18 years and 72 years
Metastatic or unresectable CD70-expressing cancer which has progressed after standard therapy
Patients may not have
Allergies or hypersensitivities to high-dose aldesleukin cyclophosphamide or fludarabine
Design
This is a phase III single center study of PBL transduced with anti-hCD70 CAR in patients with measurable unresectable cancer expressing CD70
PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 OKT3 and aldesleukin in order to stimulate T-cell growth
Transduction is initiated by exposure of these cells to retroviral vector supernatant containing replication-incompetent virus encoding the anti-hCD70 CAR
All patients will receive a non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine
On day 0 patients will receive PBL transduced with the anti-hCD70 CAR and will then begin high-dose aldesleukin
A complete evaluation of lesions will be conducted approximately 6 weeks plus or minus two weeks after treatment
The study will be conducted using a Phase III optimal design with two separate cohorts for the Phase II componentCohort 2a patients with CD70-expressing clear cell renal cell carcinoma RCC and Cohort 2b patients with a CD70-expressing non-RCC malignancy solid tumors only
A total of up to 124 patients may be required approximately 38 patients in the Phase I portion of the study and 43 41 plus an allowance of up to 2 non-evaluable patients in each cohort of the Phase II portion of the study
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 |
|---|---|---|---|
| 16-C-0131 | None | None | None |