EBV-associated Haematologic Neoplasms
Conditions
Keywords
EBV, haematologic neoplasms
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).
Interventions
BIOLOGICALAutologous monocyte - derived DCs pulsed with EBV antigen
Patients will receive approximately （5-10）x10\^6 DC vaccine via subcutaneous injections bi-weekly,totally 3-5 times.Doses 4 and 5 are designated as booster doses. The need for booster treatment and the exploration of alternative immunization schedules shall be determined by the Investigator based on the subject's condition.For subjects in the dose expansion phase, concomitant therapy recommended by the Investigator is permitted if the subject has a high tumor burden. In the event of disease progression, the Investigator is allowed to select an appropriate treatment regimen based on the subject's condition, while the subject may choose to continue receiving treatment KSD-101. If the subject declines to continue treatment KSD-101 but agrees to survival follow-up, they will be transitioned to the survival follow-up phase.
Sponsors
Tongji Hospital
Kousai Bio Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| EBV-DNA load | 1 years after DC Vaccines injection | The load levels of EBV-DNA will be detected at each time point |
| Objective response rate (ORR) | 1 years after DC Vaccines injection | The percentage of participants who achieved PR or better response |
| Disease control rate (DCR) | 1 years after DC Vaccines injection | The percentage of participants who achieved SD or better response |
| 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 |
| 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 |
| 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 |
| Levels of B cells | 1 years after DC Vaccines injection | B cells in peripheral blood will be assessed to monitor changes |
| Levels of NK cells | 1 years after DC Vaccines injection | NK cells in peripheral blood will be assessed to monitor changes |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORLi Chunrui
Tongji Hospital
Outcome results
None listed