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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
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Brief 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

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

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
Treatment Phase
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.
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
Other Name: Fludara

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
Other Name: Cytoxan

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
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

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


Contacts
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Contact: Chris DeRenzo, MD 866-278-5833 referralinfo@stjude.org

Locations
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United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Contact: Chris DeRenzo, MD    866-278-5833    referralinfo@stjude.org   
Principal Investigator: Chris DeRenzo, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
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Principal Investigator: Chris DeRenzo, MD St. Jude Children's Research Hospital
Additional Information:
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Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT04897321    
Other Study ID Numbers: 3CAR
First Posted: May 21, 2021    Key Record Dates
Last Update Posted: May 21, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Rhabdomyosarcoma
Neoplasms
Sarcoma
Neuroblastoma
Osteosarcoma
Sarcoma, Ewing
Wilms Tumor
Rhabdoid Tumor
Hepatoblastoma
Nerve Sheath Neoplasms
Neurofibrosarcoma
Desmoplastic Small Round Cell Tumor
Neoplasms, Germ Cell and Embryonal
Sarcoma, Clear Cell
Adrenal Cortex Neoplasms
Adrenocortical Carcinoma
Neuroectodermal Tumors
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Connective and Soft Tissue
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Complex and Mixed
Kidney Neoplasms