Relapsed or Refractory EBV-associated Hematological Malignancies
Conditions
Keywords
EBV, hematological malignancies
Brief summary
The main purpse of this study is to evaluate the safety and tolerability of KSD-101 in the treatment of relapsed or refractory EBV-associated hematological malignancies,to preliminarily explore the clinical efficacy ,evaluate the immune response to KSD-101 for the treatment in Patients with EBV-associated hematological diseases and the improvement in subjects' quality of life (QOL) after KSD-101 treatment.
Detailed description
This is a multi-center, single-arm, open-label, dose confirmation and expansion Phase I clinical study to evaluate the safety, tolerability, immune response, and preliminary clinical efficacy of KSD-101 in the treatment of relapsed or refractory EBV-associated hematological malignancies. The study is divided into three stages by age.
Interventions
BIOLOGICALKSD-101
Patients will receive DC vaccine via subcutaneous injections bi-weekly,total 3-5 times. KSD-101 treatment dose: The dose is tentatively set at 2.5 or 5.0 × 10\^6 cells/dose in the adult cohort.
Sponsors
Kousai Bio Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects and/or their legal guardians agree to participate and sign the ICF. 2. Male or female subjects who are 2-70 (inclusive,If the age exceeds 70 years, the decision will be made jointly by the investigator and the sponsor.) years old. 3. Subjects with histologically and/or cytologically confirmed EBV-associated hematological diseases, including but not limited to EBV-positive diffuse large B-cell lymphoma, EBV-positive NK/T-cell lymphoma, EBV-positive Hodgkin's lymphoma, EBV-positive Burkitt lymphoma, EBV-positive nodal T follicular helper (TFH) cell lymphoma (angioimmunoblastic-type), and EBV-positive primary cutaneous T-cell lymphoma, and meeting the following conditions 4. Positive for EBER by in situ hybridization (ISH or FISH) . 5. Eastern Cooperative Oncology Group (ECOG) score of 0-1. 6. The EBV-associated lymphoma population must have at least one measurable lesion (lymph node lesion with a longest diameter \> 15 mm, or extranodal lesion with a longest diameter \> 10 mm). 7. Eligible for leukapheresis and has no other contraindications for cell collection. 8. Must have adequate organ function (have not received blood transfusion or hematopoietic stimulating factor therapy within 28 days): * Hematology test: Monocyte count ≥ 0.1 × 10\^9/L, neutrophil count ≥ 1.2 × 10\^9/L, hemoglobin ≥ 90 g/L, platelet count ≥ 90 × 10\^9/L * Liver function: ALT, AST ≤ 2.5 × ULN and TBIL ≤ 1.5 × ULN \[for patients with liver metastases: ALT, AST ≤ 5 × ULN and TBIL≤ 2 × ULN\] * Kidney function: Creatinine ≤ 1.5 × ULN (if creatinine \> 1.5 ULN, creatinine clearance \> 60 mL/mins is required) (The Cockcroft-Gault formula) * Pulmonary function: pulse oximetry ≥94% * Coagulation function: Fibrinogen ≥ 1.0 g/L, activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, prothrombin time (PT) ≤ 1.5 × ULN * Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50% during the screening period 9. Male and female subjects of reproductive age agree to take non-pharmacological contraceptive measures from signing the ICF until 6 months after the last dose.
Exclusion criteria
1. Received chemotherapy or immunosuppressive therapy within 4 weeks prior to leukapheresis or radiotherapy within 2 weeks prior to leukapheresis. 2. Underwent allogeneic transplantation prior to enrollment. 3. Received (attenuated) live vaccines within 4 weeks prior to enrollment. 4. Participated in other clinical studies within 4 weeks prior to enrollment and received at least one dose of the investigational product. 5. Underwent therapeutic surgery within 4 weeks prior to enrollment, or plan to undergo major surgery during the study, except diagnostic, biopsy and drainage procedures. 6. Presence of uncontrolled infectious disease within 4 weeks prior to enrollment, except EBV infection. 7. Receiving systemic corticosteroid therapy prior to screening and require long-term systemic corticosteroids during the treatment period (except inhalation or topical application) as judged by the investigator, or received systemic corticosteroid therapy (except inhalation or topical application) within 72 hours prior to administration. 8. Active central nervous system metastases/lesions (e.g., brain edema requiring hormone intervention or brain metastases). 9. Severe cardiovascular diseases: * Grade ≥ 3 cardiovascular diseases according to the New York Heart Association (NYHA) classification within 6 months prior to enrollment. * Unstable angina or severe arrhythmias requiring medication. * Other significant ECG abnormalities, including second-degree type 2 atrioventricular block, third-degree atrioventricular block, bradycardia (ventricular rate \< 50 beats/min with clinical symptoms), etc. 10. Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and increased peripheral blood hepatitis B virus (HBV) DNA titer above the ULN; positive for hepatitis C virus (HCV) antibody and peripheral blood HCV RNA; positive for human immunodeficiency virus (HIV) antibody; positive for syphilis-specific antibodies. 11. Have not recovered to normal or Grade ≤ 1 from prior treatment-induced AEs prior to enrollment, except alopecia (any grade) and peripheral neuropathy (Grade ≤ 2). 12. Other active malignancies within the past 3 years, except for curable cancers that have been markedly cured, such as basal or squamous cell carcinoma, cervical or breast cancer in situ. 13. Prior history of severe drug allergies or history of penicillin allergy. 14. Substance abuse/addiction. 15. Women who are pregnant or nursing. 16. Other serious medical conditions, including liver disease, kidney disease, neurological/psychiatric disorders, endocrine disorders, hematologic disorders, and immune system disorders, which will render a subject unsuitable for participation in the study as judged by the investigator. 17. Other conditions that render a subject unsuitable for enrollment as judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT | The duration from the first dose to Day 28 | Incidence and number of dose-limiting toxicities. |
| adverse events (AEs) | Any adverse medical event occurring from the initiation of leukapheresis until 28 days (±7 days) after the last dose, or initiation of a new treatment (whichever occurs first) | Adverse events will be graded according to the NCI-CTCAE 6.0 grading criteria throughout the study period, except for injection site (localized) adverse events, which will be graded with reference to the Guiding Principles for Grading Adverse Events in Vaccine Clinical Trials (Revised Edition). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EBV-DNA load | The duration from the first dose to 48 weeks | Antiviral effect: changes in EBV-DNA load were assessed during the study |
| Objective response rate (ORR) | The duration from the first dose to 48 weeks | The percentage of participants who achieved PR or better response |
| Overall survival (OS) | The duration from the first dose to 48 weeks | OS is measured from the date of the initial injection of DC Vaccines to the date of the participant's death |
| Disease control rate (DCR) | The duration from the first dose to 48 weeks | The percentage of participants who achieved SD or better response |
| Progression-free survival (PFS) | The duration from the first dose to 48 weeks | The time from the start of KSD-101 treatment for the participants to the first time of disease progression or death for any reason |
| Levels of EBV-specific CD8+ T cells | The duration from the first dose to 48 weeks | EBV-specific CD8+ T cells in peripheral blood will be assessed to monitor changes |
| Levels of various lymphocyte subsets | The duration from the first dose to 48 weeks | total T lymphocytes, activated T lymphocytes, helper T lymphocytes, cytotoxic T lymphocytes, regulatory T lymphocytes, total B lymphocytes and total NK cells in peripheral blood will be assessed to monitor changes |
| EQ-5D-5L | The duration from the first dose to 48 weeks | The change from baseline in scores of EQ-5D-5L endpoints will be analyzed by age group or indication group. |
| QLQ-C30 | The duration from the first dose to 48 weeks | The change from baseline in scores of QLQ-C30 endpoints will be analyzed by age group or indication group |
Countries
China
Outcome results
None listed