A Single-arm, Open-label, Multi-center Phase I Clinical Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of KSD-101 in Patients With Relapsed or Refractory EBV-associated Hematological Malignancies
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Kousai Bio Co., Ltd.
- Enrollment
- 55
- Locations
- 2
- Primary Endpoint
- DLT
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 2 Years to 70 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects and/or their legal guardians agree to participate and sign the ICF.
- •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.
- •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
- •Positive for EBER by in situ hybridization (ISH or FISH) .
- •Eastern Cooperative Oncology Group (ECOG) score of 0-
- •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).
- •Eligible for leukapheresis and has no other contraindications for cell collection.
- •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 \[for patients with liver metastases: ALT, AST ≤ 5 × ULN and TBIL≤ 2 × ULN\]
Exclusion Criteria
- •Received chemotherapy or immunosuppressive therapy within 4 weeks prior to leukapheresis or radiotherapy within 2 weeks prior to leukapheresis.
- •Underwent allogeneic transplantation prior to enrollment.
- •Received (attenuated) live vaccines within 4 weeks prior to enrollment.
- •Participated in other clinical studies within 4 weeks prior to enrollment and received at least one dose of the investigational product.
- •Underwent therapeutic surgery within 4 weeks prior to enrollment, or plan to undergo major surgery during the study, except diagnostic, biopsy and drainage procedures.
- •Presence of uncontrolled infectious disease within 4 weeks prior to enrollment, except EBV infection.
- •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.
- •Active central nervous system metastases/lesions (e.g., brain edema requiring hormone intervention or brain metastases).
- •Severe cardiovascular diseases:
- •Grade ≥ 3 cardiovascular diseases according to the New York Heart Association (NYHA) classification within 6 months prior to enrollment.
Arms & Interventions
KSD-101
Biological: Dendritic Cell Vaccine.Autologous monocyte-derived DCs pulsed with EBV-associated antigen.
Intervention: KSD-101 (Biological)
Outcomes
Primary Outcomes
DLT
Time Frame: The duration from the first dose to Day 28
Incidence and number of dose-limiting toxicities.
adverse events (AEs)
Time Frame: 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 Outcomes
- EBV-DNA load(The duration from the first dose to 48 weeks)
- Objective response rate (ORR)(The duration from the first dose to 48 weeks)
- Overall survival (OS)(The duration from the first dose to 48 weeks)
- Disease control rate (DCR)(The duration from the first dose to 48 weeks)
- Progression-free survival (PFS)(The duration from the first dose to 48 weeks)
- Levels of EBV-specific CD8+ T cells(The duration from the first dose to 48 weeks)
- Levels of various lymphocyte subsets(The duration from the first dose to 48 weeks)
- EQ-5D-5L(The duration from the first dose to 48 weeks)
- QLQ-C30(The duration from the first dose to 48 weeks)