Multi-antigen T Cell Infusion Against Neuro-oncologic Disease

NCT03652545 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Pro00010463
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Brain Tumor

Outcome Measures

Primary Outcomes (1)

• Incidence of Product- Adverse Events

  Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.03, change from Baseline Infusion related toxicity at 42 days.

  Within 42 days of the first TAA-T dose

Secondary Outcomes (1)

• TAA-T responses

  1 year

Study Arms (1)

TAA-T

EXPERIMENTAL

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.

Biological: TAA-T

Interventions

TAA-T BIOLOGICAL

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)

TAA-T

Eligibility Criteria

• Age: 6 Months - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of high-risk CNS tumors: DIPG, high-grade glioma, medulloblastoma, ependymoma, embryonal tumors, choroid plexus carcinoma, other aggressive CNS malignancies.
• o Group A (newly diagnosed DIPG): Radiographic diagnosis with DIPG defined as tumors with a pontine epicenter and diffuse intrinsic involvement of the pons. For Group A, procurement within the first 12 weeks after completion of radiotherapy is required.
• Group B: Recurrent, progressive, or refractory disease after standard treatment. Refractory disease includes high-risk tumors with residual disease after completion of standard treatment or tumors with known poor cure rates with standard treatment.
• months to 80 years of age at enrollment
• Karnofsky/Lansky score of ≥ 60%
• Organ function:
• o ANC greater than or equal to750/µL
• o Platelets greater than or equal to 75K
• o Bilirubin less than or equal to 1.5x ULN
• o AST/ALT less than or equal to 5x ULN
• o Serum creatinine less than or equal to 1.0mg/dL or 1.5x ULN for age (whichever is higher)
• Pulse oximetry \> 90% on room air
• Agree to use contraceptive measures during study protocol participation (when age appropriate)
• Patient or parent/guardian capable of providing informed consent
• Available pre-trial tumor tissue (Optional for Group B patients, but highly encouraged. Also optional for Group A)

You may not qualify if:

• Patients with uncontrolled infections
• Patients with known HIV infection
• Pregnancy\*\* or lactating females
• Prior immunotherapy with an investigational agent within the last 28 days prior to procurement
• Patients with previous history of allogeneic stem cell transplantation (however, patients who have received autologous stem-cell infusions will remain eligible).
• Bulky tumor o Group B - patients who have bulky tumor on imaging are ineligible. These include the following: Tumor with any evidence of uncal herniation or significant midline shift Tumor with a significant brainstem component Patients who are deemed to have overly bulky tumor by the PI of the study
• Pregnancy assessment on all patients \>7 years will be performed. If patient has child bearing potential (per PI/Sub-I discretion), then pregnancy testing will be performed.
• Steroids \< 0.5 mg/kg/day dexamethasone or equivalent
• Karnofsky/Lansky score of greater than or equal to 60%
• Organ function:
• o ANC greater than or equal to750/µL
• o Platelets greater than or equal to 75K
• Bilirubin less than or equal to 1.5x ULN
• AST/ALT less than or equal to 5x ULN
• Serum creatinine less than or equal 1.0mg/dL or 1.5x ULN for age (whichever is higher)

Sponsors & Collaborators

• Catherine Bollard: lead
• Children's National Research Institute: collaborator

Study Sites (1)

Brain Tumor Institute, Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Eugene Hwang, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, center for Cancer and Immunology Research

Study Record Dates

• First Submitted: August 28, 2018
• First Posted: August 29, 2018
• Study Start: December 12, 2018
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)