What side effects are associated with this type of intervention?

The most common treatments for Diffuse Midline Glioma include radiation therapy and experimental approaches like genetically modified T cells (e.g., KIND T cells). Radiation therapy can cause side effects such as fatigue, hair loss, and skin changes. Genetically modified T cells, like KIND T cells, may lead to immune-related side effects, including cytokine release syndrome, neurotoxicity, and peritumoral neuroinflammation, which can result in severe complications such as hydrocephalus. Careful monitoring and management are essential to mitigate these risks.

What prior FDA approvals exist?

As of now, there are no specific FDA approvals mentioned in the provided context for the treatment of Diffuse Midline Glioma using genetically modified T cells like KIND T cells. However, the trial involving KIND T cells represents an innovative approach where a patient's T cells are modified to recognize tumor-specific markers, potentially offering a new avenue for treatment. Broadly, treatments for such gliomas often involve chemotherapy, radiation, and investigational therapies targeting specific genetic mutations or pathways.

What other types of research exist?

Promising novel alternatives to KIND T cells for Diffuse Midline Glioma patients include GD2-targeted CAR T cell therapy, which has shown potent antitumor efficacy in H3-K27M+ diffuse gliomas. Additionally, oncolytic viral therapy and anti-sense immunotherapy targeting cytokine TGF-beta2 are being explored for high-grade astrocytomas, which may also be relevant for DMG treatment.

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CAR T-cell Therapy

Genetically Modified T-Cells for Brain Cancer (PNOC018 Trial)

Phase 1

Recruiting

Led By Sabine Mueller, MD, PhD, MAS

Research Sponsored by University of California, San Francisco

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be younger than 65 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the safety and effectiveness of KIND T cells, which are modified immune cells, in patients with a specific type of brain tumor. The treatment involves chemotherapy to prepare for the new T cells, which are designed to better attack the cancer.

Who is the study for?

This trial is for HLA-A*0201-positive patients aged 3-21 with a specific brain tumor (H3.3K27M-mutated diffuse midline glioma) who've finished standard radiation therapy. They must not be pregnant, agree to use contraception, and have no immune disorders like HIV or hepatitis B/C. No prior treatments for the tumor are allowed.

What is being tested?

The trial tests genetically modified KIND T cells after chemotherapy drugs cyclophosphamide and fludarabine in young patients with a certain type of brain cancer. It aims to find the safest dose and see how well these engineered T cells can target and fight the tumor.

What are the potential side effects?

Potential side effects include reactions from the infusion of modified T cells, low blood cell counts due to chemotherapy, increased risk of infections, nausea, fatigue, and possible organ inflammation as an immune response.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum tolerated dose (MTD)

Number of participants with treatment-emergent adverse events

Secondary study objectives

Duration of KIND T cells in-vivo persistence

Percentage of participants who receive KIND T cells

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (KIND T cells, cyclophosphamide, fludarabine)Experimental Treatment3 Interventions

Patients receive fludarabine IV on days -4, -3, and -2 and cyclophosphamide IV on day -2 in the absence of disease progression or unacceptable toxicity for the conditioning regimen. Patients also receive KIND T cells IV at dose level 1 (2 x 106 dextramer®+ CD8+ cells/kg) on day 0. If no DLTs are reported, newly enrolling participants may receive dose level 2 of KIND T cells on day 0.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

2010

Completed Phase 4

~2310

Fludarabine

2012

Completed Phase 4

~1860

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Diffuse Midline Glioma (DMG) include radiation therapy and emerging immunotherapies like genetically modified T cells. Radiation therapy works by damaging the DNA of cancer cells, thereby inhibiting their ability to replicate and grow. Genetically modified T cells, such as KIND T cells, are engineered to recognize and attack tumor-specific markers, enhancing the immune system's ability to target and destroy cancer cells. This approach is particularly significant for DMG patients because it offers a targeted treatment option that can potentially overcome the tumor's resistance to conventional therapies, providing a new avenue for managing this aggressive cancer.