Clinical trial NCT05585996: Exploratory Clinical Study of CD19-targeted CAR-T and CAR-DC in the Treatment of Relapsed and Refractory B-cell Lymphoma
Official title: Exploratory Clinical Study of CD19-targeted CAR-T and CAR-DC in the Treatment of Relapsed and Refractory B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed and Refractory B-cell Lymphoma
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2022-10-19
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: DLT
timeFrame: Up to 28 days
measure: MTD
timeFrame: Up to 28 days
measure: Incidence of abnormalities
timeFrame: Up to 28 days
Secondary outcomes:
measure: Overall Response Rate
timeFrame: Up to 2 years
measure: Duration of Response
timeFrame: Up to 2 years
measure: Progression Free Survival
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Hanzhou
country: China
facility: 2nd Affiliated Hospital, School of Medicine, Zhejiang University
state: Zhejiang
Study officials:
affiliation: 2nd Affiliated Hospital, School of Medicine, Zhejiang Universit
name: Wenbin Qian, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: