Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT06193759 |
Other study ID # |
IMPACT |
Secondary ID |
|
Status |
Active, not recruiting |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
June 4, 2024 |
Est. completion date |
December 29, 2033 |
Study information
Verified date |
June 2024 |
Source |
Children's National Research Institute |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
This is an open-label phase 1 safety and feasibility study that will employ multi-tumor
antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically
determined personalized tumor-specific antigens (TSA) derived from a patient's primary brain
tumor tissues. Young patients with embryonal central nervous system (CNS) malignancies
typically are unable to receive irradiation due to significant adverse effects and are
treated with intensive chemotherapy followed by autologous stem cell rescue; however, despite
intensive therapy, many of these patients relapse. In this study, individualized TSA-T cells
will be generated against proteogenomically determined tumor-specific antigens after standard
of care treatment in children less than 5 years of age with embryonal brain tumors.
Correlative biological studies will measure clinical anti-tumor, immunological and biomarker
effects.
Description:
This study will be conducted at Children's National Hospital (CNH) in Washington, DC. TSA-T
products will be manufactured at the cell therapy Good Manufacturing Practice (GMP) facility
at CNH. Patients enrolled in the study will receive their infusions at CNH.
This is a phase 1 study treating children with embryonal brain tumors after definitive
resection. Residual tumor may be present at the primary site or metastatic deposits but is
not required.
Patients will be treated with standard of care therapy as required, which may include up to 3
induction chemotherapy cycles (vincristine, cyclophosphamide, cisplatin, etoposide with or
without methotrexate) and up to 3 consolidation cycles (carboplatin and thiotepa, each
followed by an infusion of autologous peripheral blood stem cells (PBSCs)). Please note:
Methotrexate will be part of the induction chemotherapy as per treating physician's
discretion.
The first TSA-T dose will be infused via a Codman Holter Rickham reservoir and catheter
(intraventricular access device) on day 0, which will ideally be within 10 days following the
patient's blood count recovery (ANC>1000, ALC>500) after the final consolidation cycle.
Patients will receive the TSA-T product as per the table below until the recommended phase 2
dose (RP2D) is reached.
Three patients will be enrolled at dose level 1 (2.5x107 cell) and monitored for at least 42
days during the safety monitoring period. If 2 DLTs are observed, the dose will be
de-escalated to dose level -1 (1x107 cells). If no DLT is observed, 3 more patients will be
enrolled at dose level 2 (5x107 cells). If 1 DLT is observed, an additional 3 patients will
be enrolled at dose level 1 (2.5x107 cell) to complete the 42-day safety monitoring period.
After these first 6 patients, an interim analysis to evaluate adverse events (AE) will occur.
If there are ≤1 DLT in these first 6 patients and no other serious safety concerns, the
remainder of the planned enrollment of 12 patients will be enrolled at dose level 2 (5x107
cells). If >1 DLT is observed in the first 6 patients, the dose will be reduced to 1x107
cells, and another 3 patients will be enrolled and monitored for the 42-day safety monitoring
period. If no further DLTs are encountered, the remainder of the planned enrollment of 12
will be enrolled at 1x107 cells. If any DLTs are observed at 1x107 cells, enrollment will be
suspended, and the Data Review Committee (DRC) will meet to determine the feasibility of a
further dose reduction. For the 3 patients treated at dose level 2 (5x107 cells), similarly
if 1 DLT is observed, additional 3 patients will be enrolled at this dose level. If >1 DLT is
observed out of the 6 patients, the dose will be de-escalated to dose level 1, and the
remainder of the patients will be enrolled at 2.5x107 cells. Each patient will receive at
least one TSA-T infusion and may receive a maximum of 8 total infusions if sufficient TSA-T
cells are available. For any infusion following the first infusion, if a patient's TSA-T
supply is insufficient to meet the dose at the enrollment dose level, the final infusion may
be administered at a lower dose level at the treating physician's discretion. The first and
second infusions will be administered at least 42 days apart and additional infusions will be
spaced at least 28 days apart. If patients have a response of stable disease or better by
iRANO criteria at the evaluation after the second infusion OR if they have clinical stability
and a clinical assessment of possible pseudoprogression on MRI despite the appearance of
radiographic progression (see below), they are eligible to receive up to 6 additional
infusions of TSA-T at a minimum of 28-day intervals as long as TSA-T cells are available.
Each additional infusion will be the same as the enrollment dose level (i.e., no subsequent
dose escalation).
Prior to the first infusion, if a patient's TSA-T supply is insufficient for the dose level
that the patient is assigned to, the patient may receive TSA-Ts at a lower dose with a
minimum of 1x107 cells. These patients will not count towards the overall safety objective
and will be replaced for that objective, although they will count towards the feasibility
objective of identifying and producing adequate TSA-T products. If patients who are
clinically stable are deemed to have possible pseudoprogression, 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 compared with the initial scan
demonstrating enlarging tumor size.