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

Metastatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03671720
• Other study ID #: TCL DC Vaccine for TMB-High
• Status: Withdrawn
• Phase: Early Phase 1
• Start date: September 11, 2018
• Est. completion date: December 30, 2022

Study information

• Verified date: February 2024
• Source: Capital Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 30, 2022
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Histologically confirmed advanced or metastatic solid tumors.

2. Patients must have received previously standard therapy for that malignancy or declined to chemotherapy/radiotherapy.

3. Estimated life expectancy > 3 months

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.

5. Age 18~75 years old

6. Next-generation sequencing identified tumor mutation burden higher than 9 Muts/MB in tumor tissue or peripheral blood samples.

7. Available for the adequate surgical or core-needle biopsy specimens from primary or metastasis lesions to manufacture the DC vaccines.

8. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

9. 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

10. 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.

Exclusion Criteria:

1. 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.

2. 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.

3. Patients with a medical or psychological impediment to probable compliance with the protocol should be excluded.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

Related Conditions & MeSH terms

• Advanced Cancer
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Biological:
• personalized DC vaccine
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.

Locations

Country	Name	City	State
China	Capital Medical University Cancer Center/Beijing Shijitan Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Capital Medical University	Duke University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Objective response rate (ORR)	The rate of patients was evaluated as complete response or partial response	6 months
Secondary	Progression-free survival of the participants(PFS)	From starting date of vaccine treatment until date of first documented disease progression or date of death from any cause, whichever comes first	24 months
Secondary	Overall survival of the participants(OS)	From starting date of vaccine treatment until date of death from any cause	24 months
Secondary	The changes in immune-response specific patient-reported outcomes(irPRO)	To assess the irPRO scale ratings prior to and after the cancer immunotherapy	24 months
Secondary	The changes in patient self-reported quality of life	To assess the EORTC QLQ-C30 scale ratings prior to and after the cancer immunotherapy	24 months