Melanoma Clinical Trial

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

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Full Description

Treatment will include a single infusion of B7-H3-CAR T cells after lymphodepleting chemotherapy, with dosing based on the number of CAR+ T cells and patient weight. The study will evaluate the safety and maximum tolerated dose (MTD) of B7-H3-CAR T cells, using a standard 3+3 study design and a 6-week evaluation period. The total study duration will be 1 year, at which point patients will enroll on our existing institutional long-term follow-up protocol.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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)

Inclusion criteria

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
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

Exclusion criteria

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)

Study is for people with:

Melanoma

Phase:

Phase 1

Estimated Enrollment:

32

Study ID:

NCT04897321

Recruitment Status:

Recruiting

Sponsor:

St. Jude Children's Research Hospital

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There is 1 Location for this study

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St. Jude Children's Research Hospital
Memphis Tennessee, 38105, United States More Info
Chris DeRenzo, MD
Contact
866-278-5833
[email protected]
Chris DeRenzo, MD
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Melanoma

Phase:

Phase 1

Estimated Enrollment:

32

Study ID:

NCT04897321

Recruitment Status:

Recruiting

Sponsor:


St. Jude Children's Research Hospital

How clear is this clinincal trial information?

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