Exploratory Clinical Study of CD19-targeted CAR-T and CAR-DC in the Treatment of Relapsed and Refractory B-cell Lymphoma
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 (0.25×106/kg, 0.5×106/kg, 0.75×106/kg ( ±20%) . CAR-T was 2×106/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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Combination therapy of CD19 CAR-T and CD19 CAR-DC 6-18 patientsare planned to be enrolled in the dose-escalation trial (0.5×10^6/kg、1×10^6/kg、2×10^6/kg和4×10^6/kg) and 52 patients in the dose-expansion trial. |
Biological: CD19 CAR-T and CD19 CAR-DC
Intravenously injected CAR DC cells and followed by CAR T cells 4 hours later
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female participants aged 18 to 75 years old at the time enrollment, with ECOG Score of ≤ 3;
-
Patients should provide a written informed consent;
-
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;
-
Life expectancy ≥ 3 months;
-
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:
-
Prior treatment that included anti-CD19-targeted therapy, CAR T cell therapy, gene therapy, and allogenic hematopoietic stem cell transplantation (allo-HSCT);
-
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;
-
Clinical trial with investigational drug was performed within 4 weeks;
-
History of other cancers;
-
Active hepatitis B or hepatitis C. Hepatitis B: HBV-DNA ≥ 1,000 IU/ml; Hepatitis C: HCV RNA positive;
-
HIV infection;
-
Uncontrollable infection of active bacteria and fungi;
-
Currently pregnant or refusal to practice birth control within 1 year;
-
Active autoimmune or inflammatory diseases;
-
Central nervous system lymphoma.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Second Affiliated Hospital, School of Medicine, Zhejiang University
Investigators
- Principal Investigator: Wenbin Qian, MD, PhD, 2nd Affiliated Hospital, School of Medicine, Zhejiang Universit
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2022-0160