Clinical trial NCT05640713: Assessment of Safety and Efficacy of ThisCART19A in Adult Patients With B Cell Malignancies After Failure of Autologous Chimeric Antigen Receptor T- Cell(CAR-T) Therapy
Official title: A Single Dose-escalation Study to Evaluate the Safety and Efficacy of Allogeneic CAR-T Targeting CD19 (ThisCART19A) in Adult Patients With B Cell Malignancies After Failure of Autologous Chimeric Antigen Receptor T- Cell(CAR-T) Therapy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Allogeneic, CAR-T, Protein Sequestration, Non-gene Edited
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Fundamenta Therapeutics, Ltd.
First posted: 2022-12-07
Enrollment: 12
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 a a phase 1, open label study to assess the safety and efficacy of ThisCART19 (Allogeneic CAR-T targeting CD19) in adult patients with B cell malignancies after failure of autologous chimeric antigen receptor T- cell(CAR-T) therapy in china.

Detailed description: This is a phase 1, single-center, nonrandomized, open-label, dose-escalation and dose expansion study to evaluate the safety and efficacy of ThisCART19A in adult patients with B cell malignancies after failure of autologous chimeric antigen receptor T- cell(CAR-T) therapy and identify a treatment regimen most likely to result in clinical efficacy while maintaining a favorable safety profile.

Eligibility criteria: Inclusion Criteria:

1. Patient with relapsed or refractory acute lymphocytic leukemia, or lymphoma；
2. No gender limitation, Age 14 years to 75 years (both upper and lower limits included)；
3. Failing to autologous CAR-T therapy；
4. Should be confirmed Cluster of differentiation(CD)19 positive；
5. The expected survival time is ≥12 weeks;
6. ECOG score 0-1;
7. Measurable or detectble disease at time of enrollment.
8. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function；

Exclusion Criteria:

1. Allergic to preconditioning measures；
2. 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；
3. Uncontrollable bacterial, fungal and viral infection during screening；
4. Patients had pulmonary embolism (PE) and/or deep vein thrombosis (DVT) within 3 months prior to enrollment;
5. Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment；
6. The presence of central nervous system involvement；
7. 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；
8. Had big lesion(single lesion diameter ≥10 cm)；
9. Receive allogeneic hematopoietic stem cell transplantation less than 100 days；
10. Vaccinated with influenza vaccine within 2 weeks prior to cleansing (SARS-COV19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included)；
11. Patients who are receiving GvHD treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion；
12. 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 B Cell Malignancy in each dose level during dose escalation stage
timeFrame: 28 days
measure: Objective Response Rate within 3 months during dose expansion stage
timeFrame: 3 months
measure: Minimum Residual Disease (MRD) Negative Remission Rate within 3 months during dose expansion stage
timeFrame: 3 months
Secondary outcomes:
measure: Duration of response(DOR) during dose escalation stage and expansion stage
timeFrame: 24 months
measure: Relapse-free Survival (RFS)
timeFrame: 24 months
measure: Event-free Survival (EFS)
timeFrame: 24 months
measure: Overall Survival (OS)
timeFrame: 24 months
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Henan cancer hospital
state: Henan
Study officials:
References: