KSD-101 Therapy for EBV-associated Lymphomas: an Exploratory Clinical Trial

Study Overview
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Brief Summary
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The main purpose of this study is to determine the tolerability and feasibility of KSD-101 in patients with EBV-associated haematologic neoplasms,to observe the characteristics of dose-limiting toxicity (DLT)and to explore the range of effective dose.

Official Title
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KSD-101 Therapy for EBV-associated Lymphomas: an Exploratory Clinical Trial

Conditions
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EBV-associated Lymphomas

Intervention / Treatment
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* Biological: (Autologous monocyte-derived DCs pulsed with allogeneic EBV-transformed B-lymphoblastoid cell line lysate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient or his legal guardian participated voluntarily and signed the informed consent form. A patient aged 18 - 70 years ( inclusive ) on the day of signing the informed consent form, male or female. A patient who is diagnosed with EBV-associated Lymphomas，and fail to respond or relapse after conventional treatment, or voluntarily choose therapeutic DC vaccines as the salvage therapy. ECOG performance score 0 - 1. Meet apheresis or intravenous blood collection criteria and no other contraindications. Adequate organ function:Hematology: neutrophils of ≥1×10^9 /L , hemoglobin of ≥ 70 g / L, platelets of ≥ 50 ×10^9 / L. Liver function: ALT, AST ≤ 3 × ULN and TBIL ≤ 1.5 × ULN.Renal function: creatinine ≤ 1.5 × ULN. Cardiac function: left ventricular ejection fraction LVEF ) ≥ 40%. Coagulation function: fibrinogen ≥ 1.0 g / L, activated partial thromboplastin time ( APTT ) ≤ 1.5 × ULN, prothrombin time ( PT ) ≤ 1.5 × ULN. A patient who has a lymph node area where subcutaneous injection can be performed. Exclusion Criteria: A patient who has received any anticancer therapy such as chemotherapy, radiotherapy or immunotherapy (eg, immunosuppressive drugs) within one month prior to screening. A female patient who is pregnant (positive urine/blood pregnancy test) or breastfeeding, or a male/female patient who plans to conceive in recent 1 year. A patient who has positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb), with positive titer of hepatitis B virus (HBV) DNA in peripheral blood; or has positive hepatitis C virus (HCV) antibody, hepatitis C virus (HCV) RNA in peripheral blood, human immunodeficiency virus (HIV) antibody, or syphilis. A patient who has central nervous system disorders (e.g., brain oedema, hormonal intervention indicated, or progression of brain metastases). Patients had an uncontrollable infectious disease within the first 4 weeks of enrollment（ except the CTCAE toxicity grade is less than 2 of genitourinary infections and upper respiratory tract infections , EBV infection） A patient who has serious underlying diseases (such as cardiovascular disease, respiratory disorder, renal insufficiency, coagulation disorder, autoimmune disease or immunodeficiency disease, etc.). A patient who has had other active malignancies within the last 3 years, unless curable and clearly cured, such as basal or squamous cell carcinoma, carcinoma in situ of cervix or breast, etc. A patient who has received prophylactic live or live-attenuated vaccines within 4 weeks prior to screening A patient who has participated in other clinical studies within 4 weeks prior to screening A patient who has a prior history of serious drug allergy or penicillin allergy. A patient who has a history of drug abuse/addiction. A patient who has any conditions resulting in ineligibility for enrollment as judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KSD-101<br>Biological: Dendritic Cell Vaccine( Autologous monocyte - derived DCs pulsed with EBV Multi-antigen) Patients will receive approximately （2.5-10）x10^6 DC vaccine via subcutaneous injections bi-weekly,totally 3-5 times. | Biological: (Autologous monocyte-derived DCs pulsed with allogeneic EBV-transformed B-lymphoblastoid cell line lysate<br>* Patients will receive approximately （2.5-10）x10^6 DC vaccine via subcutaneous injections bi-weekly,totally 3-5 times.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicity(DLT) by dose group | Dose-limiting toxicity will be assessed after injection | 1 years after DC Vaccines injection | 
| Incidence of Effective dose range by dose grouphaematologic neoplasms | Effective dose will be assessed after injection | 1 years after DC Vaccines injection | 
| Type and incidence of adverse events(AEs) and serious adverse events(SAEs) by dose group | Calculate type and incidence of adverse events(AE), serious adverse events(SAE), including those happened after injection, those related to study drug, or those that led to withdrawal from the study. They will also be aggregated by systematic organ classification(SOC), preferred term(PT), and severity. | 1 years after DC Vaccines injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EBV-DNA load | The load levels of EBV-DNA will be detected at each time point | 1 years after DC Vaccines injection | 
| Objective response rate(ORR) | The percentage of participants who achieved PR or better response | 1 years after DC Vaccines injection | 
| Disease control rate(DCR) | The percentage of participants who achieved SD or better response | 1 years after DC Vaccines injection | 
| Duration of response(DoR) | DOR will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease | 1 years after DC Vaccines injection | 
| Progression-free survival(PFS) | The time from the start of CAR-GPRC5D treatment for the participants to the first time of disease progression or death for any reason | 1 years after DC Vaccines injection | 
| Overall survival(OS) | OS is measured from the date of the initial injection of DC Vaccines to the date of the participant's death | 1 years after DC Vaccines injection | 
| Levels of EBV-specific CD8+ T cells | EBV-specific CD8+ T cells in peripheral blood will be assessed to monitor changes | 1 years after DC Vaccines injection | 
| Levels of B cells | B cells in peripheral blood will be assessed to monitor changes | 1 years after DC Vaccines injection | 
| Levels of NK cells | NK cells in peripheral blood will be assessed to monitor changes | 1 years after DC Vaccines injection |