Personalized Vaccine Generated by Autologous Dendritic Cells Pulsed With Autologous Whole Tumor Cell Lysate Treat Advanced Solid Tumor Patients With High Tumor Mutation Burden

NCT03671720 | Withdrawn Early Phase 1

• 1 other identifier: TCL DC Vaccine for TMB-High
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The study is to investigate the safety and efficacy of dendritic cells vaccines pulsed with autologous whole tumor cell lysate for treating advanced solid tumor patients with high tumor mutation burden.

Conditions

Advanced Cancer; Metastatic Cancer

Outcome Measures

Primary Outcomes (1)

• Treatment-related adverse events

  Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.All toxicities observed within 30 days of last vaccination will be included.

  12 months

Secondary Outcomes (5)

• Objective response rate (ORR)

  6 months

• Progression-free survival of the participants(PFS)

  24 months

• Overall survival of the participants(OS)

  24 months

• The changes in immune-response specific patient-reported outcomes(irPRO)

  24 months

• The changes in patient self-reported quality of life

  24 months

Study Arms (1)

personalized vaccine

EXPERIMENTAL

Biological: personalized DC vaccine

Interventions

personalized DC vaccine BIOLOGICAL

personalized vaccine comprised of autologous dendritic cells (DC) loaded in vitro with lysate from autologous tumor cells, administered intranodally on day 1,8,15, with a combination of oral cyclophosphamide (50mg) every day except the day of vaccine administrations.Cycles are repeated every 21 days. Treatment is continued until disease progression or exhaustion of vaccine supply, whichever comes first.

personalized vaccine

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed advanced or metastatic solid tumors.
• Patients must have received previously standard therapy for that malignancy or declined to chemotherapy/radiotherapy.
• Estimated life expectancy \> 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.
• Age 18\~75 years old
• Next-generation sequencing identified tumor mutation burden higher than 9 Muts/MB in tumor tissue or peripheral blood samples.
• Available for the adequate surgical or core-needle biopsy specimens from primary or metastasis lesions to manufacture the DC vaccines.
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Adequate hematologic function, with WBC ≥ 3000/microliter, hemoglobin ≥ 9 g/dL (it is acceptable to have had prior transfusion), platelets ≥ 75,000/microliter; PT-INR \<1.5 (unless patient is receiving warfarin in which case PT-INR must be \<3), PTT \<1.5X ULN
• Adequate renal and hepatic function, with serum creatinine \< 1.5 mg/dL, bilirubin \< 1.5 mg/dL (except for Gilbert's syndrome which will allow bilirubin ≤ 2.0 mg/dL), ALT and AST ≤ 2.5 x upper limit of normal.

You may not qualify if:

• Patients with a history of autoimmune disease, such as but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Autoimmune related thyroid disease and vitiligo are permitted.
• Patients with serious intercurrent chronic or acute illness, such as cardiac disease (NYHA class III or IV), hepatic disease, or other illness considered by the Principal Investigator as unwarranted high risk for investigational drug treatment.
• Patients with a medical or psychological impediment to probable compliance with the protocol should be excluded.
• Concurrent (or within the last 5 years) second malignancy other than non melanoma skin cancer, cervical carcinoma in situ, controlled superficial bladder cancer, or other carcinoma in situ that has been treated.
• Presence of an active acute or chronic infection including: a urinary tract infection, HIV (as determined by ELISA and confirmed by Western Blot). Patients with HIV are excluded based on immuno-suppression, which may render them unable to respond to the vaccine; patients with chronic hepatitis are excluded because of concern that hepatitis could be exacerbated by the injections.
• Patients on chronic steroid therapy (or other immuno-suppressives, such as azathioprine or cyclosporin A) are excluded on the basis of potential immune suppression. Patients must have had 6 weeks of discontinuation of any steroid therapy (except that used as pre-medication for chemotherapy or contrast-enhanced studies or for acute treatment (\<5 days) of intercurrent medical condition such as a gout flare) prior to enrollment.
• Pregnant and nursing women should be excluded from the protocol since this research may have unknown and harmful effects on an unborn child or on young children. If the patient is sexually active, the patient must agree to use a medically acceptable form of birth control while receiving treatment and for a period of 4 months following the last vaccination therapy. It is not known whether the treatment used in this study could affect the sperm and could potentially harm a child that may be fathered while on this study.
• Patients with acute or chronic skin disorders that will interfere with injection into the skin of the extremities or subsequent assessment of potential skin reactions will be excluded.

Sponsors & Collaborators

• Capital Medical University: lead
• Duke University: collaborator

Study Sites (1)

Capital Medical University Cancer Center/Beijing Shijitan Hospital

Beijing, Beijing Municipality, 100038, China

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Captial Medical University Cancer Center

Study Record Dates

• First Submitted: September 13, 2018
• First Posted: September 14, 2018
• Study Start: September 11, 2018
• Primary Completion: December 30, 2021
• Study Completion: December 30, 2022
• Last Updated: February 7, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)