Clinical trial NCT05350787: Evaluate the Safety, Efficacy and Pharmacokinetics of ThisCART19A in Patients With R/R B-ALL
Official title: To Evaluate the Safety, Efficacy and Pharmacokinetics of ThisCART19A in Patients With Relapsed and Refractory Acute B-cell Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
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): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
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 relapsed and refractory acute B-cell leukemia


Eligibility 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. Consistent with the diagnosis of recurrent refractory B-ALL. Recurrence： was defined as the recurrence of lymphoblasts（≥5%） in peripheral blood or bone marrow or extramedullary diseasefor patients who had acquired CR ; Refractory ：was defined as failure to CR or CRi at the end of induction therapy (generally referred to 4-week regimen or Hyper-CVAD regimen);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;

   The following factors can coexist:

   A) Failure to prepare autologous CAR-T (definition: too few autologous lymphocytes \[200/ML\] or cannot meet the release standard); B) Experienced treatment with auto car-T/berintoomumab/ CD22 antibody conjugation drugs; C) ≥100 days after hematopoietic stem cell transplantation; D) high-risk patients (High risk was defined as a high white blood cell count ≥30×109/L at diagnosis or with poor cytogenetic prognosis);
   * Hypodiploid (\<44 chromosomes);
   * KMT2A rearrangement: t (4;11) or otherwise;
   * t (v;q32)/IgH;
   * t (9;22) (q34;q11.2) or BCR-ABL1;
   * Complex karyotype (≥5 chromosomal abnormalities);
   * BCR-ABL1-like (Ph-like) ALL;

     * JAK-STAT (CRLF2r, EPORr, JAK1/2/3r, TYK2r, mutations of SH2B3, IL7r, Jak1/2/3 );
     * ABL class( rearrangement of ABL1, ABL2, PDGFRA, PDGFRB, FGFR);
     * Other (NTRKr, FLT3r, LYNr, PTK2Br);
   * Intrachromosomal amplification of chromosome 21 (IAMP21-ALL);
   * t (17;19) : TCF3-HLF fusion ;
   * Alterations of IKZF1; E) Extramedullary lesions.
5. The expected survival time is ≥12 weeks;
6. ECOG score 0-1;
7. Had good organic function during screening
8. CD19 was still expressed in leukemia cells in bone marrow, peripheral blood or biopsy tissue by flow cytometry within one month prior to informed consent (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. 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.
8. 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.
9. 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) .
10. Patients who are receiving GvHD treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion.
11. 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.
12. 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 limited toxicity(DLT) observation and the incidence of treatment-emergent adverse events(TEAE) which more than or equal to grade 3 in each dose level
timeFrame: 28 days
measure: The incidence of all grade TEAEs and ≥3 grade TEAEs
timeFrame: Up to 2 years after ThisCART19A infusion
Secondary outcomes:
measure: Objective 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
measure: MRD response rate
timeFrame: 24 months
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Hospital of Zhejiang Medical Colleage Zhejiang University
state: Zhejiang
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: