Ignite Creation Date:
2024-05-06 @ 12:00 PM
Last Modification Date:
2024-10-26 @ 12:53 PM
Study NCT ID:
NCT03652545
Status:
RECRUITING
Last Update Posted:
2023-09-21
First Post:
2018-08-28
Brief Title:
Multi-antigen T Cell Infusion Against Neuro-oncologic Disease
Sponsor:
Catherine Bollard
Organization:
Childrens National Research Institute
Study Overview
Official Title:
Phase I REsearch on Multi-antigen T Cell Infusion Against Neuro-oncologic Disease
Status:
RECRUITING
Status Verified Date:
2023-09
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:
REMIND
Brief Summary:
This Phase I dose-escalation trial is designed to determine the safety and feasibility of rapidly generated tumor multi-antigen associated specific cytotoxic T lymphocytes TAA-T in patients with newly diagnosed diffuse intrinsic pontine gliomas DIPGs Group A or recurrent progressive or refractory non-brainstem CNS malignancies Group B
Pediatric and adult patients who have high-risk CNS tumors known to typically have positivity for one or more Tumor Antigen Associated TAA WT1 PRAME andor Survivin will be eligible TAA-T will all be generated from patient peripheral blood mononuclear cells PBMC
Group A patients DIPG The first TAA-T dose will be infused any time 14 days or more after completion of radiotherapy
Group B patients other recurrentprogressiverefractory CNS tumors The first TAA-T dose will be infused any time 14 days or more after completing most recent course of conventional non-investigational therapy for their disease AND after appropriate washout periods as detailed in eligibility criteria
Pediatric and adult patients who have high-risk CNS tumors known to typically have positivity for one or more Tumor Antigen Associated TAA WT1 PRAME andor Survivin will be eligible TAA-T will all be generated from patient peripheral blood mononuclear cells PBMC
Group A patients DIPG The first TAA-T dose will be infused any time 14 days or more after completion of radiotherapy
Group B patients other recurrentprogressiverefractory CNS tumors The first TAA-T dose will be infused any time 14 days or more after completing most recent course of conventional non-investigational therapy for their disease AND after appropriate washout periods as detailed in eligibility criteria
Detailed Description:
This protocol is designed as a phase I dose-escalation study Three different TAA-T dose levels will be evaluated in each treatment group A and B see below with 2 to 4 patients enrolled at each dose level
Dose Level 1 2 x 107 cellsm2 Dose Level 2 4 x 107 cellsm2 Dose Level 3 8 x 107 cellsm2
Two patients will be initially enrolled to the lowest dose level cohort separately on each arm and followed for 42 days after initial TAA-T for DLT evaluations The decision on whether it is safe to escalate to next dose level or not will be made after at least two patients in each dose level have finished their 42-days toxicity follow up after initial TAA-T If the first two patients have not finished their 42 days follow-up up to 2 additional incoming patients can be enrolled at the current dose level
Ideally patients should not receive other systemic antineoplastic agents for at least 42 days after infusion of TAA-T for purposes of evaluation although such treatment may be added if deemed critical for patient care by the attending physician
Each patient will receive at least one TAA-T infusion and may receive a maximum of 8 subsequent infusions The first and second infusions will be administered at least 42 days apart then additional infusions will be spaced at least 28 days apart from each other The expected volume of each infusion is 1 to 10 ml
If patients with disease have a response of stable disease or better by RANO criteria at the day 28 evaluation after the second infusion OR if they have clinical stability and a clinical assessment of possible pseudoprogression on MRI they are eligible to receive up to 6 additional infusions of TAA-T at 28 day intervals if available Each subsequent infusion will be the same as the enrollment dose level ie no subsequent dose escalation The first and second infusions will be administered at least 42 days apart then additional infusions will be spaced at least 28 days apart from each other Following the first infusion if a patients TAA-T supply is insufficient for subsequent infusions at the enrollment dose level further treatments may be administered at a lower dose level at the treating physicians discretion
If patients who are clinically stable are deemed to have likely pseudoprogression at the disease evaluation after the second infusion or on subsequent imaging then these patients may still be eligible for infusion if serial imaging and clinical assessments demonstrate stability most consistent with pseudoprogression In these patients disease assessment after the imaging that first raises the concern for pseudoprogression potential progressive disease versus pseudoprogression must be at least stable when compared with the first scan demonstrating pseudoprogression
Dose Level 1 2 x 107 cellsm2 Dose Level 2 4 x 107 cellsm2 Dose Level 3 8 x 107 cellsm2
Two patients will be initially enrolled to the lowest dose level cohort separately on each arm and followed for 42 days after initial TAA-T for DLT evaluations The decision on whether it is safe to escalate to next dose level or not will be made after at least two patients in each dose level have finished their 42-days toxicity follow up after initial TAA-T If the first two patients have not finished their 42 days follow-up up to 2 additional incoming patients can be enrolled at the current dose level
Ideally patients should not receive other systemic antineoplastic agents for at least 42 days after infusion of TAA-T for purposes of evaluation although such treatment may be added if deemed critical for patient care by the attending physician
Each patient will receive at least one TAA-T infusion and may receive a maximum of 8 subsequent infusions The first and second infusions will be administered at least 42 days apart then additional infusions will be spaced at least 28 days apart from each other The expected volume of each infusion is 1 to 10 ml
If patients with disease have a response of stable disease or better by RANO criteria at the day 28 evaluation after the second infusion OR if they have clinical stability and a clinical assessment of possible pseudoprogression on MRI they are eligible to receive up to 6 additional infusions of TAA-T at 28 day intervals if available Each subsequent infusion will be the same as the enrollment dose level ie no subsequent dose escalation The first and second infusions will be administered at least 42 days apart then additional infusions will be spaced at least 28 days apart from each other Following the first infusion if a patients TAA-T supply is insufficient for subsequent infusions at the enrollment dose level further treatments may be administered at a lower dose level at the treating physicians discretion
If patients who are clinically stable are deemed to have likely pseudoprogression at the disease evaluation after the second infusion or on subsequent imaging then these patients may still be eligible for infusion if serial imaging and clinical assessments demonstrate stability most consistent with pseudoprogression In these patients disease assessment after the imaging that first raises the concern for pseudoprogression potential progressive disease versus pseudoprogression must be at least stable when compared with the first scan demonstrating pseudoprogression
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