B-NHL
Conditions
Brief summary
An evaluation of LY007 cell injection for recurrent/refractory CD20 was positive Tolerability, safety, and efficacy of B-cell non-Hodgkin lymphoma in open, single-arm Phsea I Clinical research
Detailed description
This is a phase I single-arm, open, 3+3 dose escalation study to evaluate the efficacy of LY007 cell injection Safety, tolerability, PK characteristics, PD characteristics, initial efficacy and immunogenicity. This study plans to enroll approximately 9-18 subjects with relapsed/refractory CD20-positive B-NHL, including DLBCL (inclusive Histological transformation) and TFL. The number of subjects ultimately enrolled depends on the number of DLT observed during the dose escalation phase The number of incremental dose groups prior to DLT and the determination of MTD or clinically recommended dose.
Interventions
DRUGLY007
FC and LY007 infusion
Sponsors
The First Affiliated Hospital with Nanjing Medical University
Shanghai Longyao Biotechnology Inc., Ltd.
Ruijin Hospital
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
* Participants must meet all of the following inclusion criteria to be enrolled in the study: 1. Age 18-70 years old (including 18 years old and 70 years old), regardless of gender; 2. Can understand the study and have signed the informed consent; 3. Expected survival time > 3 months; 4. The American Eastern Oncology Consortium (ECOG) score was 0-1; 5. Cd20-positive B-NHL was confirmed cytologically or histologically according to WHO 2016 criteria These include diffuse large B-cell lymphomas (including histologically transformed forms) and transformed follicular lymphomas (TFL); (For the expression status of CD20, the histological diagnosis of CD20 has been clearly documented in the past Positive subjects (diagnosis within 3 months prior to screening); Subjects without prior records, Pathological specimens provided or collected by our hospital were diagnosed as CD20 positive; Not without a clear record For those who provide or collect specimens, the researchers and sponsors will decide whether to be included according to their medical records); 6. For recurrent or refractory B-cell non-Hodgkin lymphoma, subjects must have at least been treated with anthracene Treatment with cyclodrugs and rituximab (or other CD20-targeting drugs), and have already received them At least two cycles of treatment; Refractory is defined as the best response to the most recent treatment regimen as disease progression, or the last treatment The optimal response of the regimen (at least 2 cycles) was stable disease with a duration of less than 6 months. 7. Does not meet the criteria for autologous hematopoietic stem cell transplantation (auto-HSCT) or is unwilling to perform autologous transplantation Patients with recurrence or progression after blood stem cell transplantation or autologous hematopoietic stem cell transplantation; 8. The venous access required for mononuclear cell collection can be established, and the hemoglobin is ≥70 g/L and neutral Granulocyte ≥ 1.0×109/L, platelet ≥50×109 /L, a single nucleus can be performed by the investigator's judgment Cell collection; 9. Evaluable lesions identified according to the 2014 Lugano efficacy evaluation criteria; 10. Organ functions meet the following requirements: 1. The investigator assessed sufficient bone marrow function to receive lymphocyte clearance chemotherapy; 2. Serum creatinine ≤1.5× upper limit of normal (ULN) or creatinine clearance (Cockcroft and Gault) \> 30 mL/min/1.73 m2 ; 3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× ULN (ALT and AST in patients with liver metastasis ≤5×ULN); 4. Total bilirubin ≤2.0 × ULN (for patients with Gilbert's syndrome or lymphoma invading the liver ≤3 × ULN); 5. Lung function: ≤CTCAE grade 1 dyspnea and oxygen saturation of basic finger pulse in indoor air environment Sum degree ≥92%; 6. Cardiac function: Normal diastolic function, echocardiography or radiation within 1 month prior to enrollment Sexual nuclide active angiography (MUGA) revealed left ventricular ejection fraction (LVEF) ≥ 50%, no clinically significant pericardial effusion.
Exclusion criteria
Subjects who meet any of the following criteria will not be enrolled in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events , Serious Adverse Events , Adverse Events of Particular Concern, Including cytokine release syndrome , neurotoxicity,physical examination, vital signs, ECOG score, ECG, laboratory testing, etc. | Day0 to 2year | Adverse Events , Serious Adverse Events , Adverse Events of Particular Concern, Including cytokine release syndrome , neurotoxicity,physical examination, vital signs, ECOG score, ECG, laboratory testing, etc. |
| Maximum tolerated dose or clinically recommended dose; | Day0 to 2year | No more than 1 out of 6 subjects experienced the highest dose of DLT. At least 6 subjects need to be evaluated at the MTD dose. |
| Dose limiting toxicity | Day0 to D28 | Adverse events (AEs) that meet the following criteria and occur within 28 days after the subject receives LY007 cell injection reinfusion will be classified using the ASTCT 2018 standard for CRS and neurotoxicity, while the remaining AEs will be evaluated using the CTCAE 5.0 standard: 1. Any grade 4 or 5 AE related to LY007 cell injection after treatment, excluding no clinically significant laboratory test indicators; 2. Any grade 3 AE related to LY007 cell injection that does not improve to ≤ grade 2 within 7 days after treatment, excluding laboratory test indicators with no clinical significance; 3. Any grade 3 seizures that occur after treatment and cannot be relieved to ≤ grade 2 within 3 days; 4. Any ≥ level 3 autoimmune toxicity (excluding B cell dysgenesis) that occurs after treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| therapeutic effect | Day0 to 2year | Objective response rate (ORR) evaluated according to Lugano 2014 criteria (at least 3 after cell transfusion) |
| The titer of human anti mouse antibody | Day0 to 2year | the titer of human anti mouse antibody (HAMA) in serum |
| Anti LY007 antibody | Day0 to 2year | The production of anti LY007 antibody (ADA) in serum. |
| PK aspect | Day0 to 2year | Number of LY007 cells in peripheral blood after LY007 cell administration. |
| PD aspect | Day0 to 2year | The proportion of lymphocyte subtypes in peripheral blood before and after administration of LY007 cell injection; |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory study endpoint | Day0 to 2year | The correlation between the above PK parameters and efficacy (CR, PR, SD, PD);CR=complete remission; PR=partial relief; SD=disease stability; PD=disease progression.The correlation between the expression of CD20 in peripheral blood and tumor lymph nodes at baseline and the efficacy (CR, PR, SD, PD). |
Countries
China
Contacts
Primary ContactWeili Zhao, MD
Backup ContactZixun Yan, MD
Outcome results
None listed