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

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

Interventions

DRUG

Fludarabine

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

DRUG

Cyclophosphamide

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

DRUG

MESNA

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

DRUG

B7-H3 CAR T cells

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

Sponsors & Collaborators

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Chris DeRenzo, MD · St. Jude Children's Research Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-07-06

Primary Completion

2027-03-01

Completion

2028-03-01

FDA Drug

Yes

Countries

• United States

Study Locations