Lymphoma Clinical Trial
Official title:
A Pilot Clinical Trial of Autologous EphA-2-Targeting Chimeric Antigen Receptor Dendritic Cell Vaccine Loaded With TP53 Mutant Peptide Plus ICIs for Local Advanced/Metastatic Solid Tumors or Relapsed/Refractory Lymphomas.
This is a pilot clinical trial for subjects with local advanced/metastatic solid tumors or relapsed/refractory (R/R) lymphomas to determine the safety, efficacy and immune response of autologous EphA2-targeting CAR-DC vaccine loaded with TP53 mutant peptide (TP53-EphA-2-CAR-DC) in combination with ICIs. It aims to: assess the safety and antitumor effects of TP53-EphA-2-CAR-DC vaccine; detect T cell response against TP53 mutant peptide and tumor neoepitopes after the treatment with TP53-EphA-2-CAR-DC vaccine and ICIs.
Status | Recruiting |
Enrollment | 10 |
Est. completion date | December 30, 2026 |
Est. primary completion date | December 30, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 75 Years |
Eligibility | Inclusion Criteria: 1. Age 18-75 (inclusive). 2. ECOG performance status =2 and Estimated life expectancy of more than 3 months. 3. Local advanced/metastatic solid tumors or R/R lymphomas confirmed by histopathology or cytology with documentation of tumor EphA2 positive (=20%) and TP53 mutation (R273H or R175H or R248Q or R249S) within 6 months prior to screening. The second malignancy is allowed. 4. No clinical response to standard frontline therapy or no standard therapy exists for solid tumors. Relapse after treatment with =2 lines systemic therapy or refractory disease for lymphomas. Patients who have declined standard therapy or have no access to standard therapy may be enrolled and the reasons for a lack of access need to be documented. Previous treatment with anti-PD-1/PD-L1 antibodies or anti-CTLA4 antibody are allowed, regardless of the level of PD-1/PD-L1 expression, dMMR and TMB. 5. At least one measurable lesion at baseline per RECIST version 1.1 or Lugano response criteria 2014. 6. Adequate organ function as defined by the following criteria: ANC =1000 cells/µL; Platelet count =80,000/µL; Hemoglobin =8.0 g/dL (hemocytopenia caused by lymphoma invasion of bone marrow is not subject to conditions); Serum AST and serum ALT, =3.0 x ULN (=5 x ULN for patients with liver metastases); Total serum bilirubin =3.0 x ULN); Serum creatinine =2 x ULN or creatinine clearance of =45 mL/min. 7. Willing to undergo either excised or large-needle lymph node or tissue biopsy, or provide formalin-fixed paraffin-embedded (FFPE) tumor tissue block or freshly cut unstained slides. 8. Willing to complete all scheduled visits and assessments at the institution administering the therapy. 9. Able to read, understand and provide written informed consent. Exclusion Criteria: 1. Having TP53 (R273H or R175H or R248Q or R249S) germline mutation. 2. Active central nervous system disease involvement (but allow patients with prior brain metastases treated at least 4 weeks prior to enrollment that are clinically stable and do not require intervention), or prior history of NCI CTCAE Grade =3 drug-related CNS toxicity. 3. Prior organ allograft transplantations or allogeneic hematopoietic stem cell transplantation. 4. Evidence of active uncontrolled viral, bacterial, or systemic fungal infection. 5. Known positive test result for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS). 6. Active infection of hepatitis B virus (HBV), or hepatitis C virus (HCV). 7. Patients with history (within the last 5 years) or risk of autoimmune disease who have immunosuppressive medications or immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone or equivalent) within 28 days prior to enrollment. However, patients who received a short course of corticosteroids (eg, premedication prior to antibody drug) will be eligible for study entry. 8. Major trauma or major surgery within 4 weeks prior to enrollment. 9. Previous treatment involving TP53 mutant (R273H or R175H or R248Q or R249S) and EphA2. 10. Systemic chemotherapy and other intervene within 2 weeks prior to vaccination. 11. Being participating or withdrew any other trials within 4 weeks. 12. Any serious underlying medical (eg, pulmonary, renal, hepatic, gastrointestinal, or neurological) or psychiatric condition or any issue that would limit compliance with study requirements. 13. Vaccination within 30 days of study enrollment. 14. Pregnant, lactating, or breastfeeding females. 15. Researchers believe that other reasons are not suitable for clinical trials. |
Country | Name | City | State |
---|---|---|---|
China | Biotherapeutic Department of Chinsese PLA Gereral Hospital | Beijing | Beijing |
Lead Sponsor | Collaborator |
---|---|
Chinese PLA General Hospital | Zhejiang University |
China,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Incidence of treatment related adverse events (AEs) | Determining the safety profile following the initiation of treatment and grading these toxicities by CTCAE v5.0. AEs such as cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria. | 2 years | |
Primary | Clinical Response | Clinical Response will be determined by iRECIST criteria. Response rate is the proportion of patients that achieve CR or PR. | 2 years | |
Primary | Immune Response | Immune response will be evaluated by phenotype and functional analysis of vaccine-reactive T cells and Neoantigen-reactive T cells as well as other immune cells in peripheral blood and tumor samples. Response is defined by =3 folds increase relative to pre-vaccination. | Peripheral blood: baseline, weekly before Week 9, prior to each vaccination after Week 9 until last vaccine and 1 year after last vaccine. Tumor tissue: baseline, Week 3, and following timing will be performed according to subject's condition. | |
Secondary | Progression Free Survival (PFS) | PFS is defined as the time from TP53-EphA-2-CAR-DCs infusion to documented disease progression or death. | 2 years | |
Secondary | Overall Survival (OS) | OS is defined as the time from TP53-EphA-2-CAR-DCs infusion to the date of death. | 2 years | |
Secondary | Time to response (TTR) | TTR is defined as the time from TP53-EphA-2-CAR-DCs infusion to first assessed CR or PR by investigators and based on the iRECIST criteria. | 2 years | |
Secondary | Duration of response (DOR) | DOR is defined as the time from objective response (OR) until documented tumor progression date among responders. | 2 years | |
Secondary | Number and copy number of TP53-EphA-2-CAR-DCs | Number and copy number of TP53-EphA-2-CAR-DCs were assessed by the number in peripheral blood and tumor tissue. | Peripheral blood samples are collected on days 0, 3, 7, 10, 22, the day before each vaccination until last vaccination and 1 year after last vaccine. Tumor tissues are collected at baseline, the day before Week 5, and after combination. | |
Secondary | The level of cytokines in serum | The cytokines mainly include IL-1, IL-2, IL-6, IL-8, IL-10, IL-12 (p70), TNF-a | Peripheral blood samples are collected on days 0, 3, 7, 10, 22, the days before each vaccination until last vaccination and 1 year after last vaccine. Tumor tissues are collected at baseline, the day before Week 5, and after combination. |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05540340 -
A Study of Melphalan in People With Lymphoma Getting an Autologous Hematopoietic Cell Transplant
|
Phase 1 | |
Completed |
NCT01947140 -
Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies
|
Phase 1/Phase 2 | |
Completed |
NCT00001512 -
Active Specific Immunotherapy for Follicular Lymphomas With Tumor-Derived Immunoglobulin Idiotype Antigen Vaccines
|
Phase 1 | |
Recruiting |
NCT05618041 -
The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies
|
N/A | |
Completed |
NCT01410630 -
FLT-PET/CT vs FDG-PET/CT for Therapy Monitoring of Diffuse Large B-cell Lymphoma
|
||
Active, not recruiting |
NCT04270266 -
Mind-Body Medicine for the Improvement of Quality of Life in Adolescents and Young Adults Coping With Lymphoma
|
N/A | |
Terminated |
NCT00801931 -
Double Cord Blood Transplant for Patients With Malignant and Non-malignant Disorders
|
Phase 1/Phase 2 | |
Completed |
NCT01949883 -
A Phase 1 Study Evaluating CPI-0610 in Patients With Progressive Lymphoma
|
Phase 1 | |
Completed |
NCT01682226 -
Cord Blood With T-Cell Depleted Haplo-identical Peripheral Blood Stem Cell Transplantation for Hematological Malignancies
|
Phase 2 | |
Completed |
NCT00003270 -
Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer
|
Phase 2 | |
Recruiting |
NCT05019976 -
Radiation Dose Study for Relapsed/Refractory Hodgkin/Non-Hodgkin Lymphoma
|
N/A | |
Recruiting |
NCT04904588 -
HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide
|
Phase 2 | |
Completed |
NCT04434937 -
Open-Label Study of Parsaclisib, in Japanese Participants With Relapsed or Refractory Follicular Lymphoma (CITADEL-213)
|
Phase 2 | |
Completed |
NCT01855750 -
A Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
|
Phase 3 | |
Terminated |
NCT00788125 -
Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors
|
Phase 1/Phase 2 | |
Terminated |
NCT00775268 -
18F- Fluorothymidine to Evaluate Treatment Response in Lymphoma
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT04188678 -
Resiliency in Older Adults Undergoing Bone Marrow Transplant
|
N/A | |
Terminated |
NCT00014560 -
Antibody Therapy in Treating Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
|
Phase 1 | |
Recruiting |
NCT04977024 -
SARS-CoV-2 Vaccine (GEO-CM04S1) Versus mRNA SARS-COV-2 Vaccine in Patients With Blood Cancer
|
Phase 2 | |
Active, not recruiting |
NCT03936465 -
Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitors BMS-986158 and BMS-986378 in Pediatric Cancer
|
Phase 1 |