B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)
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|ClinicalTrials.gov Identifier: NCT04897321|
Recruitment Status : Not yet recruiting
First Posted : May 21, 2021
Last Update Posted : May 21, 2021
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.
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
To evaluate the antitumor activity of B7-H3-CAR T cells
- 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
|Condition or disease||Intervention/treatment||Phase|
|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||Drug: Fludarabine Drug: Cyclophosphamide Drug: MESNA Drug: B7-H3 CAR T cells||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)|
|Estimated Study Start Date :||December 2021|
|Estimated Primary Completion Date :||March 1, 2026|
|Estimated Study Completion Date :||March 1, 2027|
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.
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
Other Name: Fludara
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
Other Name: Cytoxan
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
Other Name: Mesnex
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.
Other Name: CAR T- cell infusion
- Safety of B7-H3-CAR T cells [ Time Frame: 6 weeks after B7-H3-CAR T cell infusion ]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.
- Clinical Response [ Time Frame: 6 weeks after B7-H3-CAR T cell infusion ]The number of patients with objective responses (complete response (CR) + partial response (PR)) determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04897321
|Contact: Chris DeRenzo, MDfirstname.lastname@example.org|
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|Contact: Chris DeRenzo, MD 866-278-5833 email@example.com|
|Principal Investigator: Chris DeRenzo, MD|
|Principal Investigator:||Chris DeRenzo, MD||St. Jude Children's Research Hospital|