Clinical trial NCT05535673: Safety, Efficacy and Pharmacokinetics of ThisCART19A in Patients With Refractory or Relapsed B Cell Lymphoma
Official title: A Single Dose-escalation Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Allogeneic CAR-T Targeting CD19 in Patients With Refractory or Relapsed B Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Allogeneic, CAR-T, Protein Sequestration, Non-gene Edited, r/r B-NHL
Lead sponsor: Zhengzhou University
Sponsor class: OTHER
Collaborators: name: Fundamenta Therapeutics, Ltd.
First posted: 2022-09-10
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single dose escalation study to evaluate the safety, efficacy and pharmacokinetics of ThisCART19A (Allogeneic CAR-T targeting CD19) in patients with refractory or relapsed CD19 positive B cell Lymphoma.

Detailed description: This is a single-center, nonrandomized, open-label, dose-escalation study to evaluate the safety, efficacy and pharmacokinetics of ThisCART19A in patients with refractory or relapsed CD19 positive B cell Lymphoma, such as Diffuse large B-cell lymphoma (DLBCL) , follicular lymphoma and etc.

Eligibility criteria: Inclusion Criteria:

1. Male or female aged ≥ 18 years old;
2. Histologically confirmed diagnosis per WHO Classification Criteria for Lymphocytic Tumors 2017, including follicular lymphoma (FL), marginal zone lymphoma (MZL, including SMZL, NMZL and extranodal MZL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), etc;
3. Relapsed or refractory B-cell NHL.
4. Adequate treatment :

   1. Follicular lymphoma should be treated with at least two prior treatment including alkylating agents and anti-CD20 mAbs;
   2. Marginal zone lymphoma should be treated with at least two prior treatment including anti-CD20 mAbs;
   3. mantle cell lymphoma should be treated with a first-line therapy including anthracyclines/bendamoxetine+anti-CD20 mAbs;
   4. Diffuse large B lymphoma, not otherwise specified (DLBCL, NOS), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double/triple hit lymphoma, DHL/THL), diffuse large B-cell lymphoma (DLBCL) transformed from follicular lymphoma (FL), histological grade 3b follicular lymphoma. relapsed or primary refractory lymphoma within 12 months after first-line treatment, first-line therapy including anthracycline and anti-CD20 mAbs.
5. Failing to autologous CAR-T therapy.
6. Estimated life expectancy \> 12 weeks deemed by investigator；
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
8. At least one measurable lesion, with any nodal lesion \> 15mm in the longest diameter and any extranodal lesion \> 10mm in the longest diameter.
9. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function;
10. Should be confirmed Cluster of differentiation(CD)19 positive by biopsy for the patient who received target CD19 therapy before.

Exclusion Criteria:

1. Allergic to preconditioning measures.
2. HP-positive MALT;
3. Patients with risks of deep gastrointestinal ulcers, perforation or gastrointestinal bleeding
4. Patients with other malignancies other than B-cell malignancies within 5 years prior to screening. Patients with cured skin squamous carcinoma, basal carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be recruited.
5. Uncontrollable bacterial, fungal and viral infection during screening.
6. Patients had pulmonary embolism (PE) and/or deep vein thrombosis (DVT) within 3 months prior to enrollment.
7. Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment.
8. Imaging confirmed the presence of central nervous system involvement (both primary and secondary) and obvious symptoms at the time of screening.
9. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or Human immunodeficiency virus (HIV) or Syphilis infection. HBV-DNA \< 2000 IU/mL can be enrolled, but should admitted to use anti-virus drugs such as entecavir, tenofovir, etc, and supervisory the relative indication during the treatment.
10. Had big lesion(single lesion diameter ≥7.5 cm).
11. Receive allogeneic hematopoietic stem cell transplantation less than 100 days.
12. Vaccinated with influenza vaccine within 2 weeks prior to lymphodepleting chemotherapy (Severe Acute Respiratory Syndrome-Corona virus disease 19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included) .
13. Patients who are receiving Graft versus host disease Hepatitis(GvHD) treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion.
14. Women who are in pregnant or lactating, and female subjects or partners who plan to be pregnant within 1 year after cell infusion. Male subjects who plan pregnancy within 1 year after infusion.

Primary outcomes:
measure: Dose limited toxicity(DLT) observation in patient with NHL during dose escalation stage
timeFrame: 28 days
measure: The incidence of all grade TEAEs and ≥3 grade TEAEs during dose escalation stage
timeFrame: Up to 2 years after ThisCART19A infusion
measure: Objective Response Rate in patient with NHL during dose expansion stage
timeFrame: 12 months
Secondary outcomes:
measure: Analysis the severity and Incidence of Adverse Events in each dose level during dose escalation and dose expansion stage
timeFrame: 3 months
measure: Analysis the change characteristics of CART cell number and copy number during dose escalation and expansion stages
timeFrame: 6 months
measure: the change characteristics of immune effect cells number during dose escalation and expansion stages
timeFrame: 3 months
measure: Analysis the change characteristics of cytokines during dose escalation and expansion stages (IL-1β/IL-2/IL-4/IL-5/IL-6/IL-8/IL-10/IL-12p70/IL-17A/IL-17F/IL-22/TNF-α/TNF-β)
timeFrame: 3 months
measure: Duration of response (DOR) during dose escalation stage and expansion stage
timeFrame: 12 months
measure: Progress-free survival (PFS) during dose escalation stage and expansion stage
timeFrame: 12 months
measure: OS(overall survival) during dose escalation stage and expansion stage
timeFrame: 12 months
Other outcomes:
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