Safety and Efficacy Study for DC Vaccine in Recurrent or Progressive High-grade Gliomas

NCT06253234 | Recruiting Phase 1

• 1 other identifier: ZSKY2023-1002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open-label, multi-dose phase I clinical trial evaluating the safety, tolerability, and preliminary efficacy of ZSNeo-DC1.1, a personalized dendritic cell injection, in subjects with recurrent or progressive WHO grade III-IV gliomas post-standard treatment. The subjects are adult GBM patients who have undergone surgical resection for recurrence. After the completion of reoperation, subjects will receive autologous DC vaccine treatments as scheduled. The autologous genetic-modification-free DC cells will be loaded with multiple tumor neoantigen peptides and administered (i.h) to subjects. After 3 injections, the investigator will review subject's tolerance and compliance. The DLT observation period spans from the initial injection to 21 days after the third injection, aligning with the activation of anti-tumor immune response. About 15 subjects will be enrolled. The study utilizes a fixed dose of 1×10\^7 cells per injection and employs two immunization schedules A or B. The trial is conducted in two stages: Dose Confirmation Stage: Enrollment of six subjects with recurrent or progressive gliomas following standard treatment. Each subject receives six subcutaneous injections of ZSNeo-DC1.1. Utilization of a standard "3+3" design for fixed dose confirmation and exploration of immunization schedules A and B. Dose Expansion Stage: Enrollment of at least six subjects with recurrent or progressive gliomas post-standard treatment. Administration of six subcutaneous injections of ZSNeo-DC1.1 to each subject, further investigating the safety and preliminary efficacy of ZSNeo-DC1.1 injection.

Conditions

WHO Grade III Gliomas; WHO Grade IV Gliomas

Outcome Measures

Primary Outcomes (2)

• AE and SAE

  Evaluating the incidence rates of Adverse Events and Serious Adverse Events

  Throughout the whole clinical trial, around 2 years.

• DLT

  Dose-limiting toxicity.Referencing the results of the exploratory clinical study of ZSNeo-DC1.1 injection, clinical trial outcomes of similar drugs, and the NCI CTCAE 5.0 toxicity assessment criteria to determine DLT. The observation period for DLT is set during the activation of the subject's anti-tumor immune response, from the first day of treatment until 21 days after the third injection.

  2 months

Secondary Outcomes (5)

• Assessment of ORR (Objective Response Rate)

  For Sequence A/B, ORR is measured both on Day57, and after, ORR is measured when every 8 weeks, until the date of disease progression or death, whichever came first, assessed up to 2 years.

• Assessment of DCR (Disease Control Rate)

  For Sequence A/B, DCR is measured both on Day57, and after, ORR is measured when every 8 weeks, until the date of disease progression or death, whichever came first, assessed up to 2 years.

• Assessment of CBR (Clinical Benefit Rate)

  For Sequence A/B, CBR is measured until the date of disease progression or death, whichever came first, assessed up to 2 years.

• Assessment of PFS (Progression Free Survival)

  For Sequence A/B, PFS is measured both on Day57, and after, PFS is measured when every 8 weeks), until the date of disease progression or death, whichever came first, assessed up to 2 years.

• OS (Overall survival)

  2 years

Study Arms (2)

Treatment Sequence A

EXPERIMENTAL

Biological: personalized dendritic cell injection ZSNeo-DC1.1

Treatment Sequence B

EXPERIMENTAL

Biological: personalized dendritic cell injection ZSNeo-DC1.1

Interventions

personalized dendritic cell injection ZSNeo-DC1.1 BIOLOGICAL

Sequence A: For the first 3 cycles, 1 week as a dosing cycle, the next 3 cycles, 3 weeks as a dosing cycle, a total of 6 dosing cycles Sequence B: For the first 3 cycles, 1 week as a dosing cycle, the next 3 cycles, 2 weeks as a dosing cycle, a total of 6 dosing cycles

Also known as: DC vaccine

Treatment Sequence A; Treatment Sequence B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all the following criteria to be eligible:
• Age from 18 to 75 years (including 18 and 75 years old).
• Subjects with histologically or cytologically confirmed WHO grade III-IV gliomas experiencing recurrence or progression after standard treatment.
• Bridging therapy is allowed during the preparatory period after sample collection, with discontinuation at least 7 days or 5 drug half-lives (whichever is longer) before the initial treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2.
• Laboratory test results defining satisfactory hematological and organ function:
• Platelets (PLT) ≥ 90 × 10\^9/L; Absolute Neutrophil Count (ANC) ≥ 1.5 × 10\^9/L; Haemoglobin (HGB) ≥ 90 g/L; Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5× ULN; Total Bilirubin (TBIL) ≤ 2.5 × ULN; Albumin (ALB) ≥ 3 g/dl; Creatinine clearance rate (CrCl) ≥ 45 mL/minute or Serum Creatinine ≤ 1.5 ×ULN; International Normalized Ratio (INR), Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN; Lipase ≤ 1.5 × ULN; Amylase ≤ 1.5 × ULN; Alkaline Phosphatase (ALP) ≤ 2.5 × ULN.
• Adequate tumor and blood samples for NGS gene sequencing can be obtained through tumor reduction surgery or biopsy. Peripheral blood mononuclear cell function is normal.
• Relief of any acute, clinically significant treatment-related toxicities (excluding alopecia) to ≤ Grade 1 before the first treatment.
• Heart function: Stable hemodynamics, LVEF ≥ 50%.
• Adequate venous access for PBMC collection, with no contraindications.
• Non-surgically sterilized reproductive-age subjects must use contraception during the study and have a negative pregnancy test.
• Expected survival period \> 3 months.
• Voluntary participation, signed informed consent.
• Based on health and lab assessments, the investigator sees favorable risk-benefit for the subject in the clinical trial.

You may not qualify if:

• Subjects meeting any of the following criteria are ineligible:
• Recent participation in other drug trials, concurrent anti-tumor therapy (excluding allowed bridging therapy) within 4 weeks before initial treatment, had blood transfusions, EPO, G-CSF, or GM-CSF in the 14 days before peripheral blood mononuclear cell collection, or received live virus vaccinations within 28 days before the first treatment.
• Subjects who had camptothecin sustained-release agent implantation surgery within 6 months before the initial treatment.
• Active autoimmune diseases, prolonged use of immunosuppressive therapy, or known egg allergy.
• Positive for HIV or syphilis antibodies, or active hepatitis B or C.
• Recent systemic immunosuppressive treatment within 30 days before the initial treatment.
• Note: Short-term, systemic immunosuppressive treatment may be considered in consultation with the investigator and sponsor approval. The washout period and its duration before the initial treatment will be decided in consultation with the sponsor for these patients.
• Allowed: Inhaled glucocorticoids for COPD, salt corticosteroids (e.g., fludrocortisone) for orthostatic hypotension, and low-dose glucocorticoid supplements (≤10 mg/day prednisone or equivalent) for adrenal insufficiency.
• Uncontrolled systemic diseases, including cardiovascular diseases, organ failure, diabetes, and poorly controlled hypertension.
• Unmanageable mental illness or significant medical history that may increase risks or interfere with results.
• Thrombotic events within the first 6 months before initial treatment, unless anticoagulation can be discontinued during the screening period.
• Irreversible electrolyte imbalances.
• Severe infection in the first month before initial treatment, poorly controlled infection, or requiring antibiotic treatment within the past week (excluding prophylactic use).
• Pregnant or lactating subjects.
• Factors judged by the investigator that may necessitate premature study termination, such as non-compliance, other severe diseases requiring concurrent treatment, severe laboratory abnormalities, or family/social factors affecting subject safety or data/sample collection.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead
• ZhongSheng BioTech Inc.: collaborator

Study Sites (1)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100071, China

RECRUITING

MeSH Terms

Interventions

lentiviral minigene vaccine of COVID-19 coronavirus

Central Study Contacts

Yang Zhang, Dr

CONTACT

010; zhangyang8025@yeah.net

Xiaomin Ma

CONTACT

0518; xiaomin.ma@zskybio.com

Study Design

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

Model Details: To evaluate the safety and tolerance of personalized DC vaccine in in recurrent or progressive high-grade gliomas.

Study Record Dates

• First Submitted: February 2, 2024
• First Posted: February 12, 2024
• Study Start: February 2, 2024
• Primary Completion: June 30, 2025
• Study Completion: December 31, 2025
• Last Updated: February 11, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)