Ignite Creation Date:
2024-05-05 @ 5:30 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00466531
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-06-25
First Post:
2007-04-25
Brief Title:
Treatment of Relapsed or Chemotherapy Refractory Chronic Lymphocytic Leukemia or Indolent B Cell Lymphoma Using Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19
Sponsor:
Memorial Sloan Kettering Cancer Center
Organization:
Memorial Sloan Kettering Cancer Center
Study Overview
Official Title:
A Phase IIIa Trial For The Treatment of Relapsed or Chemotherapy Refractory Chronic Lymphocytic Leukemia or Indolent B Cell Lymphoma Using Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-06
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:
RATIONALE Using T cells from the patient that have been treated in the laboratory may help the body build an effective immune response to kill cancer cells Drugs used in chemotherapy such as cyclophosphamide work in different ways to stop the growth of cancer cells either by killing the cells or by stopping them from dividing Giving laboratory-treated T cells together with cyclophosphamide may kill more cancer cells
PURPOSE This is a two-stage protocol consisting of a single-institution phase I safety study and multi-institution phase IIa extension study
PURPOSE This is a two-stage protocol consisting of a single-institution phase I safety study and multi-institution phase IIa extension study
Detailed Description:
OBJECTIVES
Phase 1 The primary objective is to assess the safety of autologous T cells genetically modified to express chimeric antigen receptor CAR targeting CD19 antigen 19-28z with or without conditioning chemotherapy
Phase IIa The primary objective is to compare the relative engraftment and persistence of the two CAR modified CD19-targeted T cells expressing different co-stimulatory signaling domain CD28 19-28z and 4-1BB CART-19CD3z-4-1BB in the CAR construct
To compare the in vivo survival of genetically modified 19-28z CAR T cells after T cell infusion alone or in combination with conditioning chemotherapy
To compare the gene transferexpression efficiency of the two viral vectors retrovirus vs lentivirus
To assess the anti-leukemic activity of adoptively transferred CD19-targeted modified T cells linked to the CD28 19-28z and 4-1BB signaling domains CART-19CD3z-4-1BB
OUTLINE
The first stage is a standard 3-step phase I dose escalation trial to assess the safety of 19-28z CAR expressing autologous T cells with or without prior conditioning chemotherapy In Step 1 a cohort of patients will receive the lowest planned dose of 19-28z modified T cells In Step 2 a cohort of patients will receive cyclophosphamide conditioning chemotherapy followed by the lowest planned dose of 19-28z modified T cells If less than 33 of patients in the cohort Step 2 experience unanticipated dose-limiting toxicity In Step 3 a cohort of patients will be treated with the investigators choice conditioning chemotherapy followed by the higher dose of 19-28z modified T cells If less than 33 of patients in the initial cohort Step 3 experience unanticipated dose-limiting toxicity the cohort in Step 3 may be be expanded to include up to 15 patients In Step 3 an additional cohort of Waldenstroms Macroglobulinemia WM patients will be treated with the investigators choice conditioning chemotherapy followed by 19-28z T cells However to maximize safety for WM patients they will be treated at the lower dose of modified T cells 1x106 19-28z T cellskg If no toxicity is observed in the initial cohort the dose may be increased in a standard 3-step dose-escalation scheme as described above
In the Phase IIa extension part of the trial 12 patients from MSKCC will be enrolled and will be treated with co-infusion of 19-28z and CART-19CD3z-4-1BB modified T cells mixed at 11 ratio at the MTD of T cells determined from the phase I trial
Phase 1 The primary objective is to assess the safety of autologous T cells genetically modified to express chimeric antigen receptor CAR targeting CD19 antigen 19-28z with or without conditioning chemotherapy
Phase IIa The primary objective is to compare the relative engraftment and persistence of the two CAR modified CD19-targeted T cells expressing different co-stimulatory signaling domain CD28 19-28z and 4-1BB CART-19CD3z-4-1BB in the CAR construct
To compare the in vivo survival of genetically modified 19-28z CAR T cells after T cell infusion alone or in combination with conditioning chemotherapy
To compare the gene transferexpression efficiency of the two viral vectors retrovirus vs lentivirus
To assess the anti-leukemic activity of adoptively transferred CD19-targeted modified T cells linked to the CD28 19-28z and 4-1BB signaling domains CART-19CD3z-4-1BB
OUTLINE
The first stage is a standard 3-step phase I dose escalation trial to assess the safety of 19-28z CAR expressing autologous T cells with or without prior conditioning chemotherapy In Step 1 a cohort of patients will receive the lowest planned dose of 19-28z modified T cells In Step 2 a cohort of patients will receive cyclophosphamide conditioning chemotherapy followed by the lowest planned dose of 19-28z modified T cells If less than 33 of patients in the cohort Step 2 experience unanticipated dose-limiting toxicity In Step 3 a cohort of patients will be treated with the investigators choice conditioning chemotherapy followed by the higher dose of 19-28z modified T cells If less than 33 of patients in the initial cohort Step 3 experience unanticipated dose-limiting toxicity the cohort in Step 3 may be be expanded to include up to 15 patients In Step 3 an additional cohort of Waldenstroms Macroglobulinemia WM patients will be treated with the investigators choice conditioning chemotherapy followed by 19-28z T cells However to maximize safety for WM patients they will be treated at the lower dose of modified T cells 1x106 19-28z T cellskg If no toxicity is observed in the initial cohort the dose may be increased in a standard 3-step dose-escalation scheme as described above
In the Phase IIa extension part of the trial 12 patients from MSKCC will be enrolled and will be treated with co-infusion of 19-28z and CART-19CD3z-4-1BB modified T cells mixed at 11 ratio at the MTD of T cells determined from the phase I trial
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
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 |
|---|---|---|---|
| MSKCC-06138 | None | None | None |