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

Phase 1

• Conditions: EBV-associated Haematologic Neoplasms
• Interventions: Biological: Autologous monocyte - derived DCs pulsed with EBV antigen

• Registration Number: NCT05635591
• Lead Sponsor: Tongji Hospital

Brief Summary

The primary objectives of this study is to evaluate the tolerability and safety of KSD-101 in Patients with EBV-associated haematologic neoplasms, observe the dose-limiting toxicity (DLT) and and to explore the maximum tolerated dose (MTD).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-14
• Study First Submitted QC: 2022-11-22
• Study First Posted: 2022-12-02
• Study Start: 2023-01-16
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-20
• Last Update Posted: 2023-09-22
• Primary Completion: 2024-12-31
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

1. The patient or his legal guardian participated voluntarily and signed the informed consent form.
2. A patient aged 18 - 70 years ( inclusive ) on the day of signing the informed consent form, male or female.
3. A patient who is diagnosed with EBV - associated haematologic neoplasms，and fail to respond or relapse after conventional treatment, or voluntarily choose therapeutic DC vaccines as the salvage therapy.
4. ECOG performance score 0 - 1.
5. Meet apheresis or intravenous blood collection criteria and no other contraindications.
6. 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.
7. A patient who has a lymph node area where subcutaneous injection can be performed.

Exclusion Criteria

1. A patient who has received any anticancer therapy such as chemotherapy, radiotherapy or immunotherapy (eg, immunosuppressive drugs) within one month prior to screening.
2. 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.
3. 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.
4. A patient who has central nervous system disorders (e.g., brain oedema, hormonal intervention indicated, or progression of brain metastases).
5. 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）
6. A patient who has serious underlying diseases (such as cardiovascular disease, respiratory disorder, renal insufficiency, coagulation disorder, autoimmune disease or immunodeficiency disease, etc.).
7. 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.
8. A patient who has received prophylactic live or live-attenuated vaccines within 4 weeks prior to screening
9. A patient who has participated in other clinical studies within 4 weeks prior to screening
10. A patient who has a prior history of serious drug allergy or penicillin allergy.
11. A patient who has a history of drug abuse/addiction.
12. A patient who has any conditions resulting in ineligibility for enrollment as judged by the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
KSD-101	Autologous monocyte - derived DCs pulsed with EBV antigen	-

Primary Outcome Measures

Name	Time	Method
Incidence of dose-limiting toxicity (DLT) by dose group	1 years after DC Vaccines injection	Dose limiting toxicity will be assessed after injection in each dose group
Incidence of maximally tolerated dose (MTD) by dose grouphaematologic neoplasms	1 years after DC Vaccines injection	Maximally tolerated dose will be assessed after injection in each dose group
Type and incidence of adverse events (AEs) and serious adverse events (SAEs) by dose group	1 years after DC Vaccines injection	Calculate type and incidence of adverse events (AE), serious adverse event (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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Li Chunrui; 🇨🇳 Wuhan, Hubei, China