Robust Armored Dual-Cytokine (IL-15/IL-21) GPC3-CAR T Cells for Atypical Teratoid Rhabdoid Tumors and Central Nervous System Rhabdoid Tumors (RADIANT)

Plain English Summary

GPC3 CAR T Cells With IL-15 and IL-21 for Recurrent ATRT and CNS Rhabdoid Tumors (RADIANT) is a Phase 1 clinical trial sponsored by Baylor College of Medicine studying Atypical Teratoid Rhabdoid Tumor, Central Nervous System Rhabdoid Tumor. This trial tests a new type of cell therapy called CAR T-cells, which are engineered to fight specific brain tumors. It is for children aged 6 months and older with rare, aggressive brain tumors (ATRT or CNS Rhabdoid Tumors) that have returned or not responded to treatment. Participation involves receiving the experimental cell therapy and regular check-ups to monitor for side effects and effectiveness. Currently, treatment options for these aggressive tumors are limited, especially for those that have returned. The trial aims to enroll 21 participants.

Official Summary

This study is being conducted in patients with GPC3-positive brain tumors that have recurred or have not responded to standard therapy. Atypical teratoid rhabdoid tumors (ATRT) are aggressive tumors with poor outcomes and limited treatment options, particularly in young children. There is a need for new therapies that can improve outcomes while minimizing toxicity. This study evaluates a new experimental treatment using genetically engineered T cells (RADIANT-T cells) that target glypican-3 (GPC3), a protein expressed on tumor cells. These T cells are modified to express a chimeric antigen receptor (CAR) targeting GPC3, along with IL-15 and IL-21 to enhance their persistence and activity. The cells also include an inducible safety mechanism (iCasp9) that allows them to be eliminated if necessary. The purpose of this study is to determine the highest safe dose of RADIANT-T cells, evaluate their safety and side effects, assess how long they persist in the body, and determine whether they show anti-tumor activity in patients with GPC3-positive brain tumors.

Who Can Participate

Here is what you need to know about eligibility for this trial. Children aged 6 months or older with a confirmed diagnosis of GPC3-positive ATRT or CNS Rhabdoid Tumors. Tumors must have returned or not responded to previous treatments and show a specific protein (GPC3) on their surface. Patients must have a certain level of general health and function (Karnofsky/Lansky score of 60% or higher). Patients cannot have active infections (except certain Hepatitis B/C), a history of organ transplant, or be pregnant/breastfeeding. This trial is studying Atypical Teratoid Rhabdoid Tumor, Central Nervous System Rhabdoid Tumor, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how safe the new cell therapy is by tracking any severe side effects within the first 4 weeks after treatment, helping to determine the highest safe dose. The specific primary outcome measures are: Number of Participants with Dose-Limiting Toxicity (4 weeks after CAR T-cell administration). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses a critical unmet need for effective treatments for aggressive brain tumors in children, which currently have poor outcomes and limited options. This research targets Atypical Teratoid Rhabdoid Tumor, Central Nervous System Rhabdoid Tumor, where improved treatment options are needed.

Investor Insight

This trial targets a rare but aggressive pediatric cancer, representing a potential breakthrough in a niche but critical area of oncology, with early-stage research indicating a possible path to impro Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of this experimental therapy, and what to expect during treatment and recovery. Participation involves a commitment to regular hospital visits for treatment administration, monitoring, and follow-up assessments. Be prepared for potential side effects and the need for close medical supervision throughout the study. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 21 participants

Interventions

• BIOLOGICAL: 21.15.GPC3-CAR T Cells — Autologous T cells genetically engineered using retroviral vectors encoding a GPC3-specific CAR and IL-15 and IL-21 cytokines. The product also includes an inducible caspase-9 safety switch allowing pharmacologic elimination of the CAR T cells in the event of severe toxicity.

Primary Outcomes

• Number of Participants with Dose-Limiting Toxicity (4 weeks after CAR T-cell administration)

Secondary Outcomes

• Maximum Tolerated Dose (MTD) of intratumoral and/or ICV injection of 21.15.GPC3-CAR T cells in treating patients with GPC3-positive recurrent or incompletely resected ATRT. (28 days)
• Response Rate (4-6 weeks after CAR T-cell administration)

Full Eligibility Criteria

Procurement Inclusion Criteria:

* 1\) Diagnosis of GPC3-positive recurrent ATRT.
* 2\) Age ≥ 6 months
* 3\) Karnofsky/Lansky score ≥ 60%
* 4\) Informed consent explained to, understood by, and signed by patient/guardian; copy provided
* 5\) GPC3 expression by immunohistochemistry with extent score ≥ Grade 2 (\>25% positive tumor cells) and intensity score ≥ 2 (scale 0-4)

Procurement Exclusion Criteria:

* 1\) No history of organ transplantation
* 2\) No known HIV positivity
* 3\) No active bacterial, fungal, or viral infection (except Hepatitis B or Hepatitis C virus infections)
* 4\) No other risk factors in which administration of the investigational agent is deemed not in the patient's best interest, in the opinion of the investigator

Treatment Inclusion Criteria:

* 1\) Age ≥ 6 months
* 2\) Diagnosis of treatment refractory or unresectable ATRT after standard of care therapy
* 3\) Lansky/Karnofsky score ≥ 60%
* 4\) Stable neurologic exam for 7 days prior to enrollment
* 5\) Stable or decreasing dose of steroids over past 7 days prior to surgery and administration of therapy (max allowable dose is 0.1mg/kg dexamethasone or equivalent per day)
* 6\) Not receiving any concurrent anti-cancer therapy.
* 7\) At least 6 weeks following craniospinal radiation therapy.
* 8\) At least 14 days wash-out needed following small volume radiotherapy (i.e., Stereotactic Radiosurgery (SRS)).
* 9\) At least 21 days or 5 half-lives (whichever is shorter) must have elapsed since any prior systemic therapy
* 10\) Received any other forms of immunotherapy ≤ 42 days before administration of investigational agent
* 11\) At least 28 days following bevacizumab
* 12\) Creatinine clearance as estimated by Cockcroft Gault or Schwartz ≥ 60 ml/min
* 13\) Total bilirubin \< 3 times ULN for age
* 14\) INR ≤ 1.7
* 15\) Absolute neutrophil count \> 500/μl
* 16\) Platelet count \> 100,000/μl (can be transfused but must be achieved prior to enrollment)
* 17\) Hgb ≥ 7.0 g/dl (can be transfused)
* 18\) Pulse oximetry \> 90% on room air
* 19\) Recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study
* 20\) Sexually active patients must be willing to utilize one of the more effective birth control methods for 3 months after the T-cell infusion.
* 21\) Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Treatment Exclusion Criteria:

* 1\) Pregnancy or lactation (for women at child-bearing age, birth control is required)
* 2\) Uncontrolled infection
* 3\) Known HIV positivity
* 4\) Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections)
* 5\) History of organ transplantation

Trial Locations

• Texas Children's Hospital, Houston, Texas, United States

Frequently Asked Questions

Related Conditions

• Atypical Teratoid Rhabdoid Tumor
• Central Nervous System Rhabdoid Tumor
• Pediatric Brain Tumors
• Oncology
• Immunotherapy
• CAR T-cell Therapy
• Rare Cancers
• Glioblastoma
• Medulloblastoma
• Neuroblastoma

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