Adoptive Cellular Therapy for Pediatric Brain Tumors
(IMPACT Trial)
Recruiting in Palo Alto (17 mi)
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Children's National Research Institute
Must not be taking: ATG, Campath, others
Disqualifiers: Uncontrolled infections, HIV, bulky tumors, others
No Placebo Group
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot have received certain immunotherapy treatments within 28 days before the trial, and you must be on a stable or decreasing dose of steroids before receiving the TSA-T cells.
What data supports the effectiveness of the treatment Multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) for pediatric brain tumors?
Research shows that adoptive T-cell therapy, which involves using immune cells to fight cancer, has been effective in treating various solid tumors and brain tumors in experimental models. Although challenges exist, such as the tumor environment and T-cell migration, strategies are being developed to improve outcomes for brain tumors.
12345Is adoptive cellular therapy safe for humans?
Adoptive cellular therapy, including treatments like multi-antigen-targeted T cells, has been studied for safety in humans with various types of cancer, such as solid tumors and breast cancer. These studies suggest that the therapy is potentially effective and nontoxic, although some challenges like severe toxicities (e.g., cytokine release syndrome or neurotoxicity) have been noted, particularly with CAR-T cell therapies.
12678How is the treatment for pediatric brain tumors using TSA-T different from other treatments?
The TSA-T treatment is unique because it uses the patient's own immune cells, specifically T cells, that are engineered to target multiple tumor antigens, making it a more precise and potentially effective approach for eliminating cancer cells compared to traditional therapies.
123910Eligibility Criteria
This trial is for children under 5 with certain brain tumors (like medulloblastoma, pineoblastoma) who can have a device called an Ommaya reservoir placed in their brain. They should be able to handle the procedure to collect blood cells and have enough tumor tissue available. Their body must be functioning well overall, with acceptable blood counts and organ function.Inclusion Criteria
My parent or guardian can give consent for me.
My neurological condition has been stable for 2 weeks, and I agree to a short steroid treatment.
My doctor thinks I can have surgery to place a Rickham reservoir.
+6 more
Exclusion Criteria
Prior immunotherapy with an investigational agent within the last 28 days prior to procurement
I do not have any infections that aren't responding to treatment.
Patients with known HIV infection
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Standard of Care Treatment
Patients receive up to 3 induction chemotherapy cycles and up to 3 consolidation cycles with autologous stem cell rescue
12-18 weeks
TSA-T Infusion and Monitoring
Patients receive TSA-T infusions with safety monitoring for dose-limiting toxicities
42 days
Multiple visits for infusions and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment
1 year
Long-term Follow-up
Overall survival and progression-free survival are monitored
5 years
Participant Groups
The IMPACT study tests personalized immune cells (TSA-T) designed to target specific proteins on a child's own brain tumor. It's after standard treatments like chemo. The goal is to see if these custom-made cells are safe and how they affect the tumor and the child's immune system.
1Treatment groups
Experimental Treatment
Group I: Embryonal brain tumorsExperimental Treatment1 Intervention
These patients are young children (\<5 years of age) with newly diagnosed high-risk embryonal CNS malignancies and are expected to have a modest male predominance reflecting the sex-based incidence of pediatric brain tumors. Patients will have a Lansky performance status of ≥60.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Children's National HospitalWashington, United States
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Who Is Running the Clinical Trial?
Children's National Research InstituteLead Sponsor
References
Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study. [2020]Tumor-associated antigen cytotoxic T cells (TAA-Ts) represent a new, potentially effective and nontoxic therapeutic approach for patients with relapsed or refractory solid tumors. In this first-in-human trial, we investigated the safety of administering TAA-Ts that target Wilms tumor gene 1, preferentially expressed antigen of melanoma, and survivin to patients with relapsed/refractory solid tumors.
The Landscape of CAR T Cells Beyond Acute Lymphoblastic Leukemia for Pediatric Solid Tumors. [2022]Adoptive cell therapy with genetically modified T cells holds the promise to improve outcomes for children with recurrent/refractory solid tumors and has the potential to reduce treatment complications for all patients. Although T cells that express chimeric antigen receptors (CARs) specific for CD19 have had remarkable success for B-cell-derived malignancies, which has led to their approval by the U.S. Food and Drug Administration, CAR T cells have been less effective for solid tumors and brain tumors. Lack of efficacy is most likely multifactorial, but heterogeneous antigen expression; limited migration of T cells to tumor sites; and the immunosuppressive, hostile tumor microenvironment have emerged as major roadblocks that must be addressed. In this review, we summarize the clinical experience with CAR T-cell therapy for pediatric solid tumors, including brain tumors. In addition, we review strategies that have been and are being developed to enhance their antitumor activity.
[Advances in application of adoptive T-cell therapy for cancer patients]. [2023]Adoptive T-cell therapy is the administration of tumor cytotoxic T-cells derived from either patient himself or donors, which were induced or genetically engineered and expanded in vitro, and then injected into patients. Several strategies for adoptive T-cell therapy have been developed since last 30 years. From lymphokine-activated killer cells, tumor-infiltrating lymphocytes, cytokine-induced killer cells, to gene-modified T-cells and tumor associated antigen (TAA)-specific cytotoxic T-cells, the adoptive T-cell therapy has been moving forward to more precise tumor targeting and more effective in elimination of cancer cells. This article reviewed the advances of therapeutic approaches of adoptive T-cell therapy for cancer patients.
Adoptive immunotherapy of intracranial tumors by systemic transfer of tumor-draining lymph node cells (Review). [2019]T lymphocytes, reactive against tumor antigens, mediate the regression of established tumors upon adoptive transfer. We have developed an effective therapy for experimental brain tumors by systemic intravenous transfer of ex vivo activated T cells derived from tumor-draining lymph nodes. Both CD4 and CD8 T cells are required to mediate tumor regression which is exquisitely specific and confers immunologic memory. Several factors influencing the efficacy of adoptive immunotherapy for brain tumors are markedly different than for optimal treatment of tumors at other visceral sites. A similarly designed phase I clinical trial has been initiated for the treatment of malignant astrocytomas.
Systemic T cell adoptive immunotherapy of malignant gliomas. [2007]To determine the feasibility, toxicity, and potential therapeutic benefits of systemic adoptive immunotherapy, 10 patients with progressive primary or recurrent malignant glioma received this treatment. Adoptive immunotherapy, the transfer of immune T lymphocytes, is capable of mediating the regression of experimental brain tumors in animal models. In animal models, lymph nodes (LNs) that drain the tumor vaccine site are a rich source of tumor-immune T cells.
Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer. [2022]Label="Purpose" NlmCategory="UNASSIGNED">Adoptively transferred, ex vivo expanded multi-antigen-targeted T cells (multiTAA-T) represent a new, potentially effective, and nontoxic therapeutic approach for patients with breast cancer (BC). In this first-in-human trial, we investigated the safety and clinical effects of administering multiTAA T cells targeting the tumor-expressed antigens, Survivin, NY-ESO-1, MAGE-A4, SSX2, and PRAME, to patients with relapsed/refractory/metastatic BC.
CAR-T cell and Personalized Medicine. [2020]Adoptive T cell transfer (ACT) is a new era for cancer treatment, involving infusion of autologous lymphocytes. Chimeric antigen receptors (CAR) on the surface of T cells are emerging as a novel therapeutic that is giving other direction to T-cell specificity and precision medicine. T cells are engineered modification to recognize specific target antigen and are co-stimulated with intracellular signal to increase the T cell response. CAR-T cells have impressive involvement in outcome on hematological malignancies; however severe toxicities as cytokine release syndrome or neurotoxicity are a challenge to face. Solid tumors have heterogeneous antigens and tumor microenvironment that hinder CAR-T cell efficacy and increase the risk of on-target/off-tumor. Novel strategies to increase CAR-Ts specificity, safety and efficacy are ongoing in clinical trials to improve clinical outcomes in hematological and solid malignances.
[Tumor antigen-specific cytotoxic T lymphocytes and cancer immunotherapy - review]. [2016]Tumor antigen-specific cytotoxic T lymphocytes are important anti-cancer cells. The focuses of this review are to introduce the molecular basis of antigen presentation and CTL recognition, to summarize the identification of tumor associated antigens and their T cell epitopes, to highlight the current insights into the immunogenicity of TAA peptides and the principles of peptide-based vaccines against cancer, and to comment on future prospects for CTL therapy.
CAR-T cells for pediatric brain tumors: Present and future. [2021]Chimeric Antigen Receptor T (CAR-T) cells are currently approved for B cell malignancies only, in children and adults. Despite a lack of robust evidence to approve such cellular immunotherapy for pediatric solid tumors, there is a growing interest for this approach in the treatment of pediatric brain tumors. Following the identification of tumor antigens as targets, the first clinical trials demonstrated some degree of clinical and biological responses to CAR-T cells for such tumor types. Additionaly, several preclinical studies have recently identified new attractive targets and antigen combination strategies, along with a superior tumor trafficking following locoregional administration. We review here the preclinical and clinical knowledge at the basis of the current clinical development of CAR-T cells for pediatric brain tumors.
Advances in Chimeric Antigen Receptor (CAR) T-Cell Therapies for the Treatment of Primary Brain Tumors. [2022]Immunotherapy has revolutionized the care of cancer patients. A diverse set of strategies to overcome cancer immunosuppression and enhance the tumor-directed immune response are in clinical use, but have not achieved transformative benefits for brain tumor patients. Adoptive cell therapies, which employ a patient's own immune cells to generate directed anti-tumor activity, are emerging technologies that hold promise to improve the treatment of primary brain tumors in children and adults. Here, we review recent advances in chimeric antigen receptor (CAR) T-cell therapies for the treatment of aggressive primary brain tumors, including glioblastoma and diffuse midline glioma, H3 K27M-mutant. We highlight current approaches, discuss encouraging investigational data, and describe key challenges in the development and implementation of these types of therapies in the neuro-oncology setting.