RECRUITING

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

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

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

Quick Facts

Study Start:2022-07-06

Study Completion:2027-03-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04897321

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:Not specified to 21 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* 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	* 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) * 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 * Total Bilirubin ≤3 times the upper limit of normal for age, except in subjects with Gilbert's syndrome * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age * Hemoglobin≥ 7g/dL (can be transfused) * Platelet count \>50,000/uL (can be transfused) * Absolute neutrophil count (ANC) ≥ 1000/uL * Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy * 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 * If sexually active, agreement to use birth control until 3 months after T-cell infusion. Male partners should use a condom. * Available autologous transduced T-cell product that has met GMP release criteria * Agreement to participate in long-term follow-up protocol for patients, who have received genetically modified cell products * Known primary immunodeficiency * History of HIV infection * Severe, uncontrolled intercurrent bacterial, viral or fungal infection * History of hypersensitivity reactions to murine protein-containing products * Receiving systemic steroid therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone, in the 7 days prior to B7-H3-CAR T-cell infusion * Receiving systemic therapy in the 14 days prior to CAR T-cell infusion, which will interfere with the activity of the B7-H3-CAR product (in the opinion of the study PIs). * Rapidly progressing disease (in the opinion of the study PIs)

Inclusion Criteria

Exclusion Criteria

* 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

* 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)
* 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
* Total Bilirubin ≤3 times the upper limit of normal for age, except in subjects with Gilbert's syndrome
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age
* Hemoglobin≥ 7g/dL (can be transfused)
* Platelet count \>50,000/uL (can be transfused)
* Absolute neutrophil count (ANC) ≥ 1000/uL
* Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy
* 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
* If sexually active, agreement to use birth control until 3 months after T-cell infusion. Male partners should use a condom.
* Available autologous transduced T-cell product that has met GMP release criteria
* Agreement to participate in long-term follow-up protocol for patients, who have received genetically modified cell products
* Known primary immunodeficiency
* History of HIV infection
* Severe, uncontrolled intercurrent bacterial, viral or fungal infection
* History of hypersensitivity reactions to murine protein-containing products
* Receiving systemic steroid therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone, in the 7 days prior to B7-H3-CAR T-cell infusion
* Receiving systemic therapy in the 14 days prior to CAR T-cell infusion, which will interfere with the activity of the B7-H3-CAR product (in the opinion of the study PIs).
* Rapidly progressing disease (in the opinion of the study PIs)

Contacts and Locations

Study Contact

Chris DeRenzo, MD

CONTACT

866-278-5833

referralinfo@stjude.org

Principal Investigator

Chris DeRenzo, MD

PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Study Locations (Sites)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105

United States

Collaborators and Investigators

Sponsor: St. Jude Children's Research Hospital

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

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-07-06

Study Completion Date2027-03-01

Study Record Updates

Study Start Date2022-07-06

Study Completion Date2027-03-01

Terms related to this study

Additional Relevant MeSH Terms

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