Relapsed and Refractory B-cell Lymphoma
Conditions
Brief summary
This is an open, single-arm, prospective, dose-escalation clinical trial designed to evaluate the safety and the preliminary efficacy of CD19-targeted CAR-T combined with CAR-DC in the treatment of relapsed and refractory B-cell lymphoma
Detailed description
6-18 patients are planned to be enrolled in the dose-escalation trial. The dose of CD19-CAR-DC was according to the 3+3 dose-escalation principle (0.25×10\^6/kg, 0.5×10\^6/kg, 0.75×10\^6/kg ( ±20%) . CAR-T was 2×10\^6/kg . The primary endpoints are DLT, MTD, and the second endpionts are the overall response rates (CR and PR), overall survival, and progression-free survival. Based on the results in the dose-escalation trial, the recommended dose will be determined. Another 52 patients will be enrolled to continue estimating the safety and efficacy.
Interventions
BIOLOGICALCD19 CAR-T and CD19 CAR-DC
Intravenously injected CAR DC cells and followed by CAR T cells 4 hours later
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female participants aged 18 to 75 years old at the time enrollment, with ECOG Score of ≤ 3; 2. Patients should provide a written informed consent; 3. Histologically confirmed CD19+ DLBCL, HGBL-DHL, MCL, tFL, PMBL; * Confirmation obtained from central pathology review before enrollment; * Sufficient formalin-fixed, paraffin-embedded tumor samples were required for histologically confirmed diagnosis and detection of CD19 expression; * Relapsed DLBCL and tFL after ≥2 lines of chemotherapy that include rituximab and anthracycline, or refractory disease as defined in the SCHOLAR-1 study: progressive disease after receiving ≥ 4 cycles of first-line therapy or stable disease (received 2 cycles of later-line therapy) as best response to chemotherapy or relapse ≤ 12 months after autologous stem cell transplantation (ASCT); * Relapsed/refractory MCL after ≥ 2 lines of prior therapy, including immunochemotheapy and BTK inhibitor such as ibrutinib, or patient did not agree to receive BTK inhibitor treatment; * At least one measurable tumor according to revised International Working Group (IWG) Response criteria; 4. Life expectancy ≥ 3 months; 5. Adequate cardiac, pulmonary, liver, renal, and bone marrow functions, with the following laboratory values: an absolute neutrophil count \> 1,000/mm3, platelets count ≥ 45,000/mm3, and hemoglobin \> 8.0g/dl; alanine aminotransferase and aspartate aminotransferase ≤ 2.5 × the upper limit of the normal range (ULN), and total bilirubin ≤ 2.0 mg/dl; a serum creatinine of ≤ 1.5 × ULN; a left ventricular ejection fraction ≥ 50%;
Exclusion criteria
1. Prior treatment that included anti-CD19-targeted therapy, CAR T cell therapy, gene therapy, and allogenic hematopoietic stem cell transplantation (allo-HSCT); 2. Chemotherapy other than lymphodepleting chemotherapy, therapeutic doses of steroids, immunosuppressive agent, any radiation therapy or anti-tumor targeted therapy including lenalidomide, bortezomib, ibrutinib, received within 2 weeks before cell collection; 3. Clinical trial with investigational drug was performed within 4 weeks; 4. History of other cancers; 5. Active hepatitis B or hepatitis C. Hepatitis B: HBV-DNA ≥ 1,000 IU/ml; Hepatitis C: HCV RNA positive; 6. HIV infection; 7. Uncontrollable infection of active bacteria and fungi; 8. Currently pregnant or refusal to practice birth control within 1 year; 9. Active autoimmune or inflammatory diseases; 10. Central nervous system lymphoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT | Up to 28 days | To evaluate the safety, tolerability, and determine the recommended dosage of combined therapy of CD19 CAR-T and CD19 CAR-DC for Relapsed/Refractory B-cell Non-Hodgkin Lymphoma |
| MTD | Up to 28 days | MTD was the highest dose for DLT in ≤1/6 subjects |
| Incidence of abnormalities | Up to 28 days | Incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Up to 2 years | The proportion of CR or PR patients as assessed by investigators based on Lugano 2014 Response Assessment |
| Duration of Response | Up to 2 years | The time from the start of the first assessment of CR or PR to the first assessment as disease recurrence or progression or death |
| Progression Free Survival | Up to 2 years | The length of time that a participant's disease did not progress during or after CAR-T treatment. |
Countries
China
Contacts
Primary ContactWenbin Qian, PhD
Backup ContactWen Lei, PhD
Outcome results
None listed