Ignite Creation Date:
2025-12-24 @ 3:40 PM
Ignite Modification Date:
2025-12-25 @ 1:50 PM
Study NCT ID:
NCT05238792
Status:
RECRUITING
Last Update Posted:
2024-12-31
First Post:
2022-02-03
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Multi Tumor-Associated Antigen-Specific T Lymphocytes to Treat Patients with High Risk Solid Tumors
Sponsor:
Children's National Research Institute
Organization:
Study Overview
Official Title:
Phase I Research Study Utilizing Allogeneic Multi Tumor-Associated Antigen-Specific T Lymphocytes to Advance the Care of Patients with High-Risk Solid Tumors
Status:
RECRUITING
Status Verified Date:
2024-12
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:
This is a phase I dose-escalation study to evaluate the safety of partially human leukocyte antigen (HLA)-matched multi tumor-associated antigen-specific T cell (TAA-T) therapy for patients with high-risk solid tumors due to the presence of refractory, relapsed and/or minimal residual detectable disease following conventional therapy. Conventional therapy may include chemotherapy, surgery, radiation, autologous stem cell transplant, or targeted therapy.
Detailed Description:
In this dose escalation trial, three dose levels, with two arms dependent on age, will be tested for safety. Arm A will enroll patients age ≥18 years and \<70 years and Arm B will enroll patients age ≥6 years and \<18 years. TAA-T product will first be administered to patients as monotherapy at dose level 1 to determine safety. Following demonstration of safety in dose level 1, lymphodepleting chemotherapy will be administered prior to the first dose of TAA-Ts on the dose escalation phase (dose levels 2 and 3). The TAA-T product will be assessed for safety and anti-tumor activity.
Description of Study Intervention:
The treatment schedule is as follows: Patients will receive an infusion of partially HLA-matched TAA-T any time \>1 week after completing most recent course of conventional (non-investigational) therapy for their disease. For the lymphodepletion cohort, patients will receive lymphodepletion (LD) chemotherapy \>2 weeks from most recent course of conventional therapy and will nadir and recover before beginning TAA-T therapy. Patients will be enrolled to one of the following TAA-T dose levels:
BSA \<1.20 BSA ≥1.20 Dose level 1 without LD (low dose) 2x107 cells 4x107 cells Dose level 2 (LD + Low dose) 2x107 cells 4x107 cells Dose level 3 (LD + High dose) 4x107 cells 8x107 cells
There will be separate study arms for adult (Arm A) and pediatric (Arm B) patients:
Arm A Age ≥18 years and \<70 years Arm B Age ≥6 years and \<18 years Enrollment will first be restricted to Arm A on dose level 1 (DL1). Following demonstration of safety, enrollment will start on dose level 2 (DL2) on Arm A for an additional 3 patients and we will contact the U.S Food and Drug Administration (FDA) with the safety data from the first 3 adults treated on DL1 to initiate enrollment on Arm B. Following demonstration of safety on Arm A at DL2, we will open enrollment to all patients (Arm A and B). Three patients will be enrolled at each dose level until the maximum tolerated dose (MTD) is determined, at which point to ensure safety, a total of 6 patients will be treated at the MTD.
One additional dose of TAA-Ts can be administered without lymphodepleting chemotherapy from day 45 after the initial infusion if there is a partial response (based on response evaluation criteria in solid tumors (RECIST)) or no response with stable disease, or if the patient receives immunosuppressive therapy that would compromise TAA-T persistence after the first infusion (such as corticosteroids), and if the patient has not experienced dose-limiting toxicities related to the study product and meets eligibility criteria for the additional infusion. Each patient will receive at least one TAA-T infusion and may receive a maximum of 2 doses. The first and second doses will be administered a minimum of 45 days apart. The expected volume of each infusion is 1 to 10 cc, though may be greater in larger patients. Dose escalation will occur once at least 3 patients on each study arm have completed the 45 day follow up period following their first TAA-T infusion. Response will be monitored after the first infusion at day 45, then at day 28 after subsequent infusion if administered.
Description of Study Intervention:
The treatment schedule is as follows: Patients will receive an infusion of partially HLA-matched TAA-T any time \>1 week after completing most recent course of conventional (non-investigational) therapy for their disease. For the lymphodepletion cohort, patients will receive lymphodepletion (LD) chemotherapy \>2 weeks from most recent course of conventional therapy and will nadir and recover before beginning TAA-T therapy. Patients will be enrolled to one of the following TAA-T dose levels:
BSA \<1.20 BSA ≥1.20 Dose level 1 without LD (low dose) 2x107 cells 4x107 cells Dose level 2 (LD + Low dose) 2x107 cells 4x107 cells Dose level 3 (LD + High dose) 4x107 cells 8x107 cells
There will be separate study arms for adult (Arm A) and pediatric (Arm B) patients:
Arm A Age ≥18 years and \<70 years Arm B Age ≥6 years and \<18 years Enrollment will first be restricted to Arm A on dose level 1 (DL1). Following demonstration of safety, enrollment will start on dose level 2 (DL2) on Arm A for an additional 3 patients and we will contact the U.S Food and Drug Administration (FDA) with the safety data from the first 3 adults treated on DL1 to initiate enrollment on Arm B. Following demonstration of safety on Arm A at DL2, we will open enrollment to all patients (Arm A and B). Three patients will be enrolled at each dose level until the maximum tolerated dose (MTD) is determined, at which point to ensure safety, a total of 6 patients will be treated at the MTD.
One additional dose of TAA-Ts can be administered without lymphodepleting chemotherapy from day 45 after the initial infusion if there is a partial response (based on response evaluation criteria in solid tumors (RECIST)) or no response with stable disease, or if the patient receives immunosuppressive therapy that would compromise TAA-T persistence after the first infusion (such as corticosteroids), and if the patient has not experienced dose-limiting toxicities related to the study product and meets eligibility criteria for the additional infusion. Each patient will receive at least one TAA-T infusion and may receive a maximum of 2 doses. The first and second doses will be administered a minimum of 45 days apart. The expected volume of each infusion is 1 to 10 cc, though may be greater in larger patients. Dose escalation will occur once at least 3 patients on each study arm have completed the 45 day follow up period following their first TAA-T infusion. Response will be monitored after the first infusion at day 45, then at day 28 after subsequent infusion if administered.
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?: