B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

NCT04897321 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 3CARNCI-2021-10933
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

3CAR is being done to investigate an immunotherapy for patients with solid tumors. It is a Phase I clinical trial evaluating the use of autologous T cells genetically engineered to express B7-H3-CARs for patients ≤ 21 years old, with relapsed/refractory B7-H3+ solid tumors. This study will evaluate the safety and maximum tolerated dose of B7-H3-CAR T cells.The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give to patients with B7-H3-positive solid tumors. Primary objective To determine the safety of one intravenous infusion of autologous, B7-H3-CAR T cells in patients (≤ 21 years) with recurrent/refractory B7-H3+ solid tumors after lymphodepleting chemotherapy Secondary objective To evaluate the antitumor activity of B7-H3-CAR T cells Exploratory objectives

• To evaluate the tumor environment after treatment with B7-H3-CAR T cells
• To assess the immunophenotype, clonal structure and endogenous repertoire of B7-H3-CAR T cells and unmodified T cells
• To characterize the cytokine profile in the peripheral blood after treatment with B7-H3-CAR T cells

Conditions

Pediatric Solid Tumor; Osteosarcoma; Rhabdomyosarcoma; Neuroblastoma; Ewing Sarcoma; Wilms Tumor; Adrenocortical Cancer; Desmoplastic Small Round Cell Tumor; Germ Cell Cancer; Rhabdoid Tumor; Clear Cell Sarcoma; Hepatoblastoma; Melanoma; Carcinoma; Malignant Peripheral Nerve Sheath Tumors; Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• Safety of B7-H3-CAR T cells

  A phase I design to determine the maximum tolerated dose (MTD) of autologous, B7-H3-CAR T cells. Four dose levels (3x10\^5/kg, 1x10\^6/kg, 3x10\^6/kg, and 1x10\^7/kg) will be evaluated.

  6 weeks after B7-H3-CAR T cell infusion

Secondary Outcomes (1)

• Clinical Response

  6 weeks after B7-H3-CAR T cell infusion

Study Arms (1)

Treatment Phase

OTHER

During the treatment phase, the participant receives an infusion of the B7-H3-CAR T cells that were made in the Collection and Manufacturing Phase. Chemotherapy is given for several days prior to the cellular infusion. Patients are then monitored for possible side effects, as well as effects of the treatment on their cancer.

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: MESNA; Drug: B7-H3 CAR T cells

Interventions

Fludarabine DRUG

Fludarabine phosphate is a synthetic purine nucleoside analog. It acts by inhibiting DNA polymerase, ribonucleotide reductase and DNA primase by competing with the physiologic substrate, deoxyadenosine triphosphate, resulting in inhibition of DNA synthesis. Intravenous

Also known as: Fludara

Treatment Phase

MESNA DRUG

Mesna is a synthetic sulfhydryl (thiol) compound. Mesna contains free sulfhydryl groups that interact chemically with urotoxic metabolites of oxaza-phosphorine derivatives such as cyclophosphamide and ifosfamide

Also known as: Mesnex

Treatment Phase

Cyclophosphamide DRUG

Cyclophosphamide is a nitrogen mustard derivative. It acts as an alkylating agent that causes cross-linking of DNA strands by binding with nucleic acids and other intracellular structures, thus interfering with the normal function of DNA. Intravenous

Also known as: Cytoxan

Treatment Phase

B7-H3 CAR T cells DRUG

The study participant will receive B7-H3-CAR T cells by vein, through either an IV or a central line.

Also known as: CAR T- cell infusion

Treatment Phase

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Procurement and T-cell production eligibility\*
• \*a previously collected, autologous leukapheresis product can be used for T-cell production
• Age ≤21 years old
• B7-H3+ solid tumor with measurable disease; B7-H3 expression will be evaluated by standard immunohistochemistry (IHC) using a previously obtained biopsy; a tumor is considered B7-H3 positive with an H-score ≥100
• Estimated life expectancy of \>12 weeks
• Karnofsky or Lansky (age-dependent) performance score ≥50
• For females of child bearing age:
• Not pregnant with negative serum pregnancy test within 7 days prior to enrollment
• Not lactating with intent to breastfeed
• Meets eligibility criteria to undergo autologous apheresis, or have previously undergone autologous apheresis

You may not qualify if:

• Known primary immunodeficiency
• Known HIV positivity
• Severe intercurrent bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection)
• History of hypersensitivity reactions to murine protein-containing products
• Rapidly progressive disease (in the opinion of the study PIs)
• Treatment eligibility
• Age ≤21 years old
• B7-H3+ solid tumor with measurable disease
• Evidence of relapsed or refractory disease after standard first-line therapy
• Estimated life expectancy of \>8 weeks
• Karnofsky or Lansky (age-dependent) performance score≥50
• Echocardiogram with a ventricular ejection fraction
• \>40%; or shortening fraction ≥25%
• Adequate renal function defined as creatinine clearance or radioisotope GFR 50 ml/min/1.73m2 (GFR 40 ml/min/1.73m2 if \< 2 years of age)
• Adequate pulmonary function defined as pulse oximetry ≥92% on room air or forced vital capacity (FVC) ≥50% of predicted value

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Osteosarcoma; Rhabdomyosarcoma; Neuroblastoma; Sarcoma, Ewing; Wilms Tumor; Adrenal Cortex Neoplasms; Desmoplastic Small Round Cell Tumor; Neoplasms, Germ Cell and Embryonal; Rhabdoid Tumor; Sarcoma, Clear Cell; Hepatoblastoma; Melanoma; Carcinoma; Neurofibrosarcoma; Sarcoma

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; Mesna

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Myosarcoma; Neoplasms, Muscle Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neurofibroma; Nerve Sheath Neoplasms; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids

Study Officials

• Chris DeRenzo, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chris DeRenzo, MD

CONTACT

866-278-5833; referralinfo@stjude.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2021
• First Posted: May 21, 2021
• Study Start: July 6, 2022
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)