Safety and Efficacy of CAR-T Cell Therapy for Relapsed/refractory Neuroblastoma and Desmoplastic Small Round Cell Tumors: a Single-arm, Open-label Trial.

NCT06836505 | Recruiting Phase 1 DMC

• 1 other identifier: TXEC-2024-025
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

Title: Safety and efficacy of CAR-T cell therapy for relapsed/refractory neuroblastoma and desmoplastic small round cell tumors: a single-arm, open-label trial. The CART used in this study will be provided by Shanghai YaKe Biotechnology Ltd. Aims:

1. 1.To evaluate the safety and efficacy of GD2/B7H3 CAR-T therapy for relapsed/refractory neuroblastoma, and observe its pharmacokinetic/pharmacodynamic characteristics and the survival of CAR-T cells in relapsed/refractory neuroblastoma patients.
2. 2.To evaluate the safety and efficacy of GD2/B7H3 CAR-T therapy for relapsed/refractory desmoplastic small round cell tumor, and observe its pharmacokinetic/pharmacodynamic characteristics and the survival of CAR-T cells in desmoplastic small round cell tumor patients.

Conditions

Neuroblastoma (NB); Desmoplastic Small Round Cell Tumor (DSRCT)

Keywords

CART, Neuroblastoma, Desmoplastic Small Round Cell Tumor

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety of CAR-T cells in relapsed/refractory neuroblastoma and desmoplastic small round cell tumor patients.

  1. To evaluate the safety of the infusion of CAR T cells at different escalating/deescalating doses and establish the dose limiting toxicity (DLT) of the cellular product. Toxicity will be evaluated according to the CTC AE scale, version 4.0. DLT will be defined as any of the following that is not pre-existing, due to infection or to underlying malignancy and that may be considered possibly, probably or definitely related to the study cellular products. (1) Non-hematologic DLT is any grade 3 or 4 non-hematologic toxicity; (2) Hematologic DLT is defined as any grade 4 hematologic toxicity related to infusion ; (3) Grade 4 reactions related to infusion; (4) Death related to CAR T cells infusions. The incidence of grade 3-5 toxicities, with a main attention to severe Cytokine Release Syndrome (CRS), will be evaluated. 2. To determine the optimal dose of CAR transduced T cells resulting in the control of the disease without inducing unacceptable levels of toxicity (MTD) .

  From enrollment to the end of treatment at 1 year

Secondary Outcomes (1)

• To evaluate the efficacy of CAR-T cells in relapsed/refractory neuroblastoma and desmoplastic small round cell tumor patients.

  From enrollment to the end of treatment at 1 year

Study Arms (1)

Safety and efficacy of CAR-T cell therapy for relapsed/refractory NB and DSRCT

EXPERIMENTAL

Biological: CART therapy

Interventions

CART therapy BIOLOGICAL

GD2/B7H3 CAR T-cell therapy

Safety and efficacy of CAR-T cell therapy for relapsed/refractory NB and DSRCT

Eligibility Criteria

• Age: 1 Year - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients who are diagnosed as relapsed/refractory neuroblastoma or relapsed/refractory desmoplastic small round cell tumors;
• Age 1-50 years, any gender;
• Agree to participate in the trial and sign a written informed consent form;
• Expected survival of ≥12 weeks;
• Karnofsky performance status (for patients ≥16 years) or Lansky performance status (for patients \<16 years) (Appendix 1) must be at least 50;
• Good function of major organs:
• Liver function: ALT ≤ 5 times the upper limit of normal for the corresponding age, and bilirubin ≤ 2.0 mg/dL, except for patients with Gilbert-Meulengracht syndrome. Patients with Gilbert-Meulengracht syndrome who have bilirubin ≤ 3.0 times the upper limit of normal and direct bilirubin ≤ 1.5 times the upper limit of normal may be included;
• Renal function: Plasma creatinine ≤ 1.5 times the upper limit of normal, or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m²;
• Pulmonary function: Oxygen saturation ≥ 95% in room air;
• Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 45%;
• Patients using the following medications must meet the following conditions:
• Steroids: Steroid treatment doses must be stopped at least 2 weeks before CAR-T infusion. However, physiological replacement doses of steroids are allowed; Immunosuppressants: Any immunosuppressive drugs must be stopped at least 4 weeks before enrollment; Anti-proliferative treatments other than lymphodepleting chemotherapy within two weeks before infusion; CNS disease prophylaxis must be stopped 1 week prior to CAR-T infusion (e.g., intrathecal methotrexate injection);
• Patients of childbearing potential (both male and female) must agree to use reliable contraception methods (hormonal or barrier methods or abstinence) with their partner until at least 12 months after CAR-T cell infusion, and until two consecutive flow cytometry or PCR tests show no CAR-T cells in the body;
• If the subject cannot provide suitable T cells for CAR-T preparation, T cells from a healthy donor may be collected for preparation.

You may not qualify if:

• Patients with any of the following items will not be enrolled in this study:
• Patients with increased intracranial pressure or altered consciousness;
• Patients who have received radiation therapy within 2 weeks prior to infusion;
• Patients with active hepatitis B (defined as HBV DNA \> 500 IU/mL) or hepatitis C (HCV RNA positive);
• HIV-positive patients or patients with a positive syphilis test;
• Patients with uncontrolled acute life-threatening bacterial, viral, or fungal infections (e.g., positive blood cultures within ≤72 hours before infusion);
• Patients with unstable angina and/or myocardial infarction within 6 months prior to screening;
• Patients with a history of or concurrent malignancies, except for the following conditions:
• Basal cell carcinoma or squamous cell carcinoma that has been adequately treated (sufficient wound healing required before study enrollment);
• Carcinoma in situ of the cervix or breast that has been cured, with no signs of recurrence for at least 3 years before the study;
• Primary malignant tumors that have been completely resected and have been in complete remission for ≥5 years;
• Pregnant or breastfeeding female patients;
• Patients with uncontrolled arrhythmias that have not been managed medically;
• Patients who need oral anticoagulation therapy within 1 week before CAR-T cell infusion;
• Patients with active neuroautoimmune or inflammatory diseases (e.g., Guillain-Barré syndrome, amyotrophic lateral sclerosis);

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Yake Biotechnology Ltd.: collaborator
• Dongguan Taixin Hospital: collaborator

Study Sites (3)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Dongguan Taixin Hospital

Dongguan, Guang, 523125, China

RECRUITING

Shanghai YaKe Biotechnology Ltd.

Shanghai, Shanghai Municipality, 200438, China

RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Desmoplastic Small Round Cell Tumor

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Sarcoma; Neoplasms, Connective and Soft Tissue

Study Officials

• Yizhuo Zhang

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yizhuo Zhang, PhD

CONTACT

020-87342460; zhangyzh@sysucc.org.cn

Suying Lu, PhD

CONTACT

lusy@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: January 25, 2025
• First Posted: February 20, 2025
• Study Start: December 12, 2024
• Primary Completion (Estimated): December 12, 2027
• Study Completion (Estimated): December 12, 2027
• Last Updated: February 26, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)