Ignite Creation Date:
2024-05-06 @ 8:20 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06343376
Status:
RECRUITING
Last Update Posted:
2024-05-17
First Post:
2024-03-25
Brief Title:
Genetically Engineered Cells EGFRt19-28zIL-12 CAR T Cells for the Treatment of Relapsed or Refractory CD19 Hematologic Malignancies
Sponsor:
Roswell Park Cancer Institute
Organization:
Roswell Park Cancer Institute
Study Overview
Official Title:
A Phase I Trial of CD19-Targeted Chimeric Antigen Receptor CAR Modified T Cells Genetically Engineered to Secrete Interleukin 12 IL-12 and With a Truncated Human Epidermal Growth Factor Receptor EGFRt in Patients With Relapsed or Refractory CD19 Hematologic Malignancies
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial tests the safety side effects and best dose of genetically engineered cells called EGFRt19-28zIL-12 CAR T cells and to see how they work in treating patients with hematologic malignancies that makes a protein called CD19 CD19-positive that has come back after a period of improvement relapsed or that has not responded to previous treatment refractory Chimeric Antigen Receptor CAR T-cell Therapy is a type of treatment in which a patients T cells a type of immune system cell are changed in the laboratory so they will attack cancer cells T cells are taken from a patients blood Then the gene for a special receptor that binds to a certain protein on the patients cancer cells is added to the T cells in the laboratory The special receptor is called a chimeric antigen receptor CAR Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers To improve the effectiveness of the modified T cells and to help the immune system fight cancer cells better the modified T cells given in this study will include a gene that makes the T cells produce a cytokine a molecule involved in signaling within the immune system called interleukin-12 IL-12 The researchers think that IL-12 may improve the effectiveness of the modified T cells and it may also strengthen the immune system to fight cancer Giving EGFRt19-28zIL-12 CAR T cells may be safe and tolerable in treating patients with relapsed or refractory CD19 hematologic malignancies
Detailed Description:
PRIMARY OBJECTIVE
I To determine the safety toxicity and maximum tolerated dose MTD of EGFRt19-28zIL-12 CAR T-lymphocytes EGFRt19-28zIL-12 CAR T cells in patients with relapsed or refractory CD19 aggressive hematologic malignancies
SECONDARY OBJECTIVES
I To assess the anti-tumor efficacy of adoptively transferred EGFRt19-28zIL-12 T cells
II To assess the in vivo persistence of adoptively transferred EGFRt19-28zIL-12 T cells
EXPLORATORY OBJECTIVES
I To describe the cellular and cytokine microenvironment following infusion of adoptively transferred EGFRt19-28zIL-12 T cells
II To characterize endogenous anti-tumor immune responses following infusion of adoptively transferred EGFRt19-28zIL-12 T cells
III To summarize levels of normal B cells and the incidence of B cell aplasia following infusion of adoptively transferred EGFRt19-28zIL-12 T cells
IV To determine the proportion of evaluable patients who achieve minimal residual disease MRD-negativity in peripheral blood andor bone marrow
V To assess phenotype and in vitro function of end-of-production EOP EGFRt19-28zIL-12 CAR T cells and phenotype at recovery following CAR T cell administration
OUTLINE This is a dose-escalation study of EGFRt19- 28zIL-12 CAR T cells Patients are assigned to 1 of 2 cohorts
COHORT A Patients undergo leukapheresis prior to treatment Patients receive EGFRt19- 28zIL-12 CAR T cells intravenously IV over 5 to 30 minutes on day 0 Patients also undergo echocardiography ECHO or multigated acquisition scan MUGA during screening Patients also undergo computed tomography CT or positron emission tomography PET as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial Additionally patients undergo a tissue biopsy during screening and on the trial
COHORT B Patients undergo leukapheresis prior to treatment and receive lymphodepletion chemotherapy with cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes on days -5 -4 and -3 Patients then receive EGFRt19- 28zIL-12 CAR T cells IV over 5 to 30 minutes on day 0 Patients also undergo ECHO or MUGA during screening Patients also undergo CT or PET as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial Additionally patients undergo a tissue biopsy during screening and on the trial
After completion of study treatment patients are followed up weekly for 4 weeks every 4 weeks until 24 months every 3 months thereafter for 1 year then annually for up to 5 years followed by long-term follow up for up to 15 years
I To determine the safety toxicity and maximum tolerated dose MTD of EGFRt19-28zIL-12 CAR T-lymphocytes EGFRt19-28zIL-12 CAR T cells in patients with relapsed or refractory CD19 aggressive hematologic malignancies
SECONDARY OBJECTIVES
I To assess the anti-tumor efficacy of adoptively transferred EGFRt19-28zIL-12 T cells
II To assess the in vivo persistence of adoptively transferred EGFRt19-28zIL-12 T cells
EXPLORATORY OBJECTIVES
I To describe the cellular and cytokine microenvironment following infusion of adoptively transferred EGFRt19-28zIL-12 T cells
II To characterize endogenous anti-tumor immune responses following infusion of adoptively transferred EGFRt19-28zIL-12 T cells
III To summarize levels of normal B cells and the incidence of B cell aplasia following infusion of adoptively transferred EGFRt19-28zIL-12 T cells
IV To determine the proportion of evaluable patients who achieve minimal residual disease MRD-negativity in peripheral blood andor bone marrow
V To assess phenotype and in vitro function of end-of-production EOP EGFRt19-28zIL-12 CAR T cells and phenotype at recovery following CAR T cell administration
OUTLINE This is a dose-escalation study of EGFRt19- 28zIL-12 CAR T cells Patients are assigned to 1 of 2 cohorts
COHORT A Patients undergo leukapheresis prior to treatment Patients receive EGFRt19- 28zIL-12 CAR T cells intravenously IV over 5 to 30 minutes on day 0 Patients also undergo echocardiography ECHO or multigated acquisition scan MUGA during screening Patients also undergo computed tomography CT or positron emission tomography PET as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial Additionally patients undergo a tissue biopsy during screening and on the trial
COHORT B Patients undergo leukapheresis prior to treatment and receive lymphodepletion chemotherapy with cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes on days -5 -4 and -3 Patients then receive EGFRt19- 28zIL-12 CAR T cells IV over 5 to 30 minutes on day 0 Patients also undergo ECHO or MUGA during screening Patients also undergo CT or PET as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial Additionally patients undergo a tissue biopsy during screening and on the trial
After completion of study treatment patients are followed up weekly for 4 weeks every 4 weeks until 24 months every 3 months thereafter for 1 year then annually for up to 5 years followed by long-term follow up for up to 15 years
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?:
True
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2024-01818 | REGISTRY | None | None |
| I-3641523 | OTHER | Roswell Park Cancer Institute | None |