Clinical trial NCT05350852: Evaluate the Safety, Efficacy and Pharmacokinetics of ThisCART19A in Patients With MRD+ B-ALL
Official title: To Evaluate the Safety, Efficacy and Pharmacokinetics of ThisCART19A in Patients With MRD Positive Acute B-cell Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: B-ALL
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2022-04-28
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is an open label, phase I study to assess the safety, efficacy and pharmacokinetics of ThisCART19A in patients with MRD+ B-ALL


Eligibility criteria: Inclusion Criteria:

* Inclusion Criteria:

  1. All subjects or legal representatives must sign a voluntary letter of consent approved by the IRB in person prior to the commencement of any screening procedure;
  2. Patients diagnosed with B-ALL according to the Chinese Guidelines for the Diagnosis and Treatment of Adult Acute Lymphoblastic Leukemia (2021 edition);
  3. There is no gender limitation, age 18-65 (upper limit not included);
  4. Disease status ≥CR2 with bone marrow flow cytometry MRD≥0.1%.
  5. Patients with Ph+ R/R ALL who failed after 2-line TKI treatment, were intolerant to TKI treatment or were not suitable for TKI treatment;
  6. The expected survival time is ≥12 weeks;
  7. ECOG score 0-1;
  8. Had good organic function during screening
  9. CD19 was still expressed on leukemia cells in bone marrow, peripheral blood or biopsy tissue by flow cytometry, results within one month prior to informed consent are acceptable (after the last treatment).

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 within 3 months prior to enrollment.
5. Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment.
6. Imaging confirmed the presence of central nervous system involvement (both primary and secondary) and obvious symptoms at the time of screening.
7. \< 100 days after hematopoietic stem cell transplantation.
8. Active HBV or HCV or HIV or Syphilis infection. HBV-DNA \< 2000 IU/mL can be enrolled, but should admitted to use anti-virus drugs such as entecavir, tenufovir, etc, and supervisory the relative indication during the treatment.
9. Combined systemic steroid use (e.g., prednisone ≥20mg) within 3 days prior to screening. Or systemic diseases that require long-term use of immunization Inhibitor.
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.
13. Any ineligibility conditions considered by the investigator that may increase the risk of the subject or interfere with the results of the study.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Up to 28 days after ThisCART19A infusion
measure: The incidence of all grade TEAEs and ≥3 grade TEAEs
timeFrame: Up to 2 years after ThisCART19A infusion
Secondary outcomes:
measure: Relapse-Free Survival
timeFrame: 24 months
measure: MRD response rate
timeFrame: At Month 1, 2, 3
measure: The change characteristics of chimeric antigen receptor(CAR)-T cell number and copy number in patients after infusion
timeFrame: 3 months
measure: Changes in cytokine level after ThisCART19A infusion.
timeFrame: 3 months
measure: Changes in immune effect cells count after ThisCART19A infusion.
timeFrame: 3 months
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first affiliated hospital of medical college of zhejiang university
state: Zhejiang
Study officials:
affiliation: The first hospital affiliated Zhejiang University
name: He Huang, Doctor
role: PRINCIPAL_INVESTIGATOR
References: