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

ConditionsPediatric Solid TumorOsteosarcomaRhabdomyosarcomaNeuroblastomaEwing SarcomaWilms TumorAdrenocortical CancerDesmoplastic Small Round Cell TumorGerm Cell CancerRhabdoid TumorClear Cell SarcomaHepatoblastomaMelanomaCarcinomaMalignant Peripheral Nerve Sheath TumorsSoft Tissue Sarcoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
AgeUp to 21
SponsorSt. Jude Children's Research Hospital

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • 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

  • 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

  • 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

  • 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.

Treatment groups

48 Participants
are divided into 1 treatment group
Group A: Treatment PhaseOther 4 interventions

Trial outcomes

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.

Time frame
6 weeks after B7-H3-CAR T cell infusion

Secondary outcomes

1

Clinical Response

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.

Time frame
6 weeks after B7-H3-CAR T cell infusion

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

St. Jude Children's Research Hospital

Lead sponsor

Source ClinicalTrials.gov
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