Multi-antigen T Cell Infusion Against Neuro-oncologic Disease (REMIND)
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|ClinicalTrials.gov Identifier: NCT03652545|
Recruitment Status : Recruiting
First Posted : August 29, 2018
Last Update Posted : July 21, 2021
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 and/or 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 recurrent/progressive/refractory 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.
|Condition or disease||Intervention/treatment||Phase|
|Brain Tumor||Biological: TAA-T||Phase 1|
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 cells/m2 Dose Level 2: 4 x 107 cells/m2 Dose Level 3: 8 x 107 cells/m2
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 (i.e. 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 patient's 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 physician's 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I REsearch on Multi-antigen T Cell Infusion Against Neuro-oncologic Disease|
|Actual Study Start Date :||December 12, 2018|
|Estimated Primary Completion Date :||March 2023|
|Estimated Study Completion Date :||May 2024|
Three different dosing schedules will be evaluated.
Dose Level One: 2 x 107 cells/m2 Dose Level Two: 4 x 107 cells/m2 Dose Level Three: 8 x 107 cells/m2
Group A patients (DIPG): The first TAA-T dose will be infused any time more than or equal to 14 days after completion of radiotherapy.
Group B patients (other recurrent/progressive/refractory CNS tumors): TAA-T will be infused any time more than or equal to 14 days after completing most recent course of conventional (non-investigational) therapy for their disease AND after appropriate washout periods as detailed in eligibility criteria.
Ideally, patients should not receive other systemic antineoplastic agents for at least 42 days after the infusion of TAA-T, although such treatment may be added if deemed critical for patient care by the attending physician.
Patients with newly diagnosed diffuse intrinsic pontine gliomas DIPGs (Group A) or recurrent, progressive, or refractory non-brainstem CNS malignancies (Group B). The goal of this cell infusion will be to initiate an immune response against brain tumors that includes multiple antigens and may prevent tumor evasion (through decreased expression of a single antigen)
- Incidence of Product- Adverse Events [ Time Frame: Within 42 days of the first TAA-T dose ]Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.03, change from Baseline Infusion related toxicity at 42 days.
- TAA-T responses [ Time Frame: 1 year ]Determine the number of patients who respond to tumor associated antigen lymphocytes from base line to one year.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03652545
|Contact: Eugene Hwang, MD||(202) 476 5046||EHwang@childrensnational.org|
|Contact: Fahmida Hoq, MBBS, MSfirstname.lastname@example.org|
|United States, District of Columbia|
|Brain Tumor Institute, Children's National Medical Center||Recruiting|
|Washington, District of Columbia, United States, 20010|
|Contact: Eugene Hwang, MD 202-476-5046 email@example.com|
|Principal Investigator:||Eugene Hwang, MD||Children's National Health System|