Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressing Autologous T Cells as an Immunotherapy for Children With Solid Tumors (CARE)

Plain English Summary

Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors is a Phase 1 clinical trial sponsored by Baylor College of Medicine studying Liver Cancer, Rhabdomyosarcoma, Malignant Rhabdoid Tumor, Liposarcoma, Wilms Tumor, Yolk Sac Tumor. This trial tests a new type of T-cell therapy called CARE T cells, which are engineered to find and kill cancer cells. It is for children and young adults up to age 21 with certain solid tumors that have returned, not responded to treatment, or cannot be treated with standard options. Participation involves receiving the CARE T-cell infusion and regular check-ups to monitor for side effects and treatment response. Alternative treatments may include standard chemotherapy, radiation, surgery, or other targeted therapies, depending on the specific cancer. The trial aims to enroll 24 participants.

Official Summary

Patients may be considered if the cancer has come back, has not gone away after standard treatment or the patient cannot receive standard treatment. This research study uses special immune system cells called CARE T cells, a new experimental treatment. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients. Investigators have found from previous research that they can put a new gene (a tiny part of what makes-up DNA and carries a person's traits) into T cells that will make them recognize cancer cells and kill them. In the lab, investigators made several genes called a chimeric antigen receptor (CAR), from an antibody called GPC3. The antibody GPC3 recognizes a protein found solid tumors including pediatric liver cancers. This CAR is called GPC3-CAR. To make this CAR more effective, investigators also added two genes that includes IL15 and IL21, which are protein that helps CAR T cells grow better and stay in the blood longer so that they may kill tumors better. The mixture of GPC3-CAR and IL15 plus IL21 killed tumor cells better in the laboratory when compared with CAR T cells that did not have IL15 plus IL21 .This study will test T cells that investigators made (called genetic engineering) with GPC3-CAR and the IL15 plus IL21 (CARE T cells) in patients with GPC3-positive solid tumors. T cells made to carry a gene called iCasp9 can be killed when they encounter a specific drug called AP1903. The investigato

Who Can Participate

Here is what you need to know about eligibility for this trial. Children and young adults aged 1 to 21 years with specific solid tumors that have a marker called GPC3 on their cancer cells. Patients must have tumors that have returned or not responded to previous treatments, and be well enough to tolerate the treatment (e.g., good organ function, adequate blood counts). Individuals with a history of organ transplants, known HIV, or active infections (except certain types of Hepatitis B or C) may not be eligible. Patients who have had reactions to certain antibody treatments in the past might also be excluded. This trial is studying Liver Cancer, Rhabdomyosarcoma, Malignant Rhabdoid Tumor, Liposarcoma, Wilms Tumor, Yolk Sac Tumor, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how many patients experience dose-limiting toxicities, which helps doctors understand the safest dose of the new therapy. The specific primary outcome measures are: Number of Patients with Dose Limiting Toxicity (4 weeks). 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 aims to fill a gap in treating aggressive pediatric solid tumors by using a patient's own immune cells, enhanced to specifically target and destroy cancer cells. This research targets Liver Cancer, Rhabdomyosarcoma, Malignant Rhabdoid Tumor, Liposarcoma, Wilms Tumor, Yolk Sac Tumor, where improved treatment options are needed.

Investor Insight

This early-phase trial explores a novel CAR T-cell therapy for pediatric solid tumors, a market with significant unmet needs, suggesting potential for future investment if successful. Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of CARE T-cell therapy for your child's type of cancer. Understand what the treatment process involves, including the time commitment for infusions and follow-up appointments. Discuss how your child's cancer will be monitored during and after the treatment. This trial is currently recruiting participants. 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: 24 participants

Interventions

• GENETIC: CARE T cells — Four different dosing schedules will be evaluated. The following dose levels will be evaluated: DL0: 1x10\^7/m\^2 DL1: 3x10\^7/m\^2 DL2: 1x10\^8/m\^2 DL3: 3x10\^8/m\^2 The doses are calculated according to the actual number of GPC3-CAR transduced T cells.

Primary Outcomes

• Number of Patients with Dose Limiting Toxicity (4 weeks)

Secondary Outcomes

• Percent of Patients with best response as either complete remission or partial remission (4 weeks)
• Median T cell persistence (15 years)
• Manufacturing feasibility of 21.15.GBBz T cells (3 years)

Full Eligibility Criteria

Procurement Eligibility

Inclusion Criteria:

* Diagnosis of GPC3-positive\* solid tumors (as determined by immunohistochemistry with an extent score of \>=Grade 2 \[\>25% positive tumor cells\] and an intensity score of \>= 2 \[scale 0-4\]).
* Age ≥1 year and ≤ 21 years
* Lansky or Karnofsky score ≥60%
* Life expectancy ≥16 weeks
* Barcelona Clinic Liver Cancer Stage A, B or C (for patients with hepatocellular carcinoma only)
* Child-Pugh-Turcotte score \<7 (for patients with hepatocellular carcinoma only)
* Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Exclusion Criteria:

* History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies).
* History of organ transplantation
* Known HIV positivity
* Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections)

Treatment Eligibility

Inclusion Criteria:

* Age ≥ 1 year and ≤ 21 years
* Barcelona Clinic Liver Cancer Stage A, B or C (for patients with hepatocellular carcinoma only)
* Lansky or Karnofsky score ≥ 60%
* Child-Pugh-Turcotte score \< 7 (for patients with hepatocellular carcinoma only)
* Adequate organ function:
* Creatinine clearance as estimated by Cockcroft Gault or Schwartz ≥ 60 ml/min
* Total bilirubin \< 3 times ULN for age
* INR ≤1.7 (for patients with hepatocellular carcinoma only)
* Absolute neutrophil count \> 750/µl
* Platelet count \> 75,000/µl (Needs to be confirmed prior to treatment whether with or without transfusion)
* Hgb ≥ 8.0 g/dl (Needs to be confirmed prior to treatment whether with or without transfusion)
* Pulse oximetry ≥ 92% on room air
* Incurable disease after treatment with up- front therapy (Patients who have relapsed disease despite a standard of care salvage therapy)
* Wash out period, such that patient has recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study, and returned to their clinical baseline, as determined by history and physical exam.
* Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the T-cell infusion.
* Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Exclusion Criteria:

* Pregnancy or lactation
* Uncontrolled infection
* Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day, dose adjustment or discontinuation of medication must occur at least 24 hours prior to CAR T cell infusion)
* Known HIV positivity
* Active bacterial, fungal or viral infection \[except Hepatitis B (HBV patients with active disease who meet the criteria for anti-HBV therapy should be on a suppressive antiviral therapy prior to initiation of cancer therapy) or Hepatitis C virus infections (should have completed curative antiviral treatment with HCV viral load below the limit of quantification\]
* Congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis
* Active autoimmune or inflammatory disorder
* Live vaccines within 30 days prior to enrollment
* History of organ transplantation
* History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)

Trial Locations

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

Frequently Asked Questions

Related Conditions

• Liver Cancer
• Rhabdomyosarcoma
• Malignant Rhabdoid Tumor
• Liposarcoma
• Wilms Tumor
• Yolk Sac Tumor
• Pediatric Solid Tumors
• Hepatocellular Carcinoma
• Relapsed Cancers
• Refractory Cancers

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