Clinical trial NCT04788472: Sequential CD19 and CD22 CAR-T Therapy for Newly Diagnosed Ph+ B-ALL
Official title: Clinical Trial for the Efficacy and Safety of Sequential CD19 and CD22 CAR-T Therapy for Adult Patients with Newly Diagnosed Ph Chromosome Positive B-cell Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: B-Cell Acute Lymphoblastic Leukemia, Adult
Keywords: CD19 CAR-T
CD22 CAR-T
Ph Chromosome Positive
B-ALL
Newly diagnosed
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2021-03-09
Enrollment: 28
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: Clinical Trial for the Efficacy and Safety of Sequential CD19 and CD22 CAR-T Therapy for Adult Patients With Newly Diagnosed Ph Chromosome Positive B-cell Acute Lymphoblastic Leukemia

Detailed description: This study was designed as a prospective, open-label, single-center study. It aims to evaluate the efficacy and safety of CD19 CAR-T cells in combination with dasatinib for the treatment of newly diagnosed Ph-positive B-cell acute lymphoblastic leukemia in adult.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years old;
2. Subjects with a diagnosis of B-cell acute lymphoblastic leukemia according to the 2016 edition of the WHO classification criteria for acute leukemia;
3. Subjects whose chromosomal and fusion gene analysis showed positivity for the Ph chromosome, BCR/ABL1 fusion gene;
4. Leukemia cells were CD19 and CD22 positive;
5. Patients with newly diagnosed B-ALL were not treated with standard chemotherapy regimens;
6. Serum total bilirubin ≤ 51 mol/L, serum ALT and AST both ≤ 3 times the upper limit of the normal range, blood creatinine ≤ 176.8 mol/L;
7. Echocardiography showed a left ventricular ejection fraction (LVEF) ≥50%;
8. Subjects had no active pulmonary infection and oxygen saturation ≥92% without oxygen;
9. The prognosis for survival is more than 3 months;
10. ECOG score 0-2;
11. Subjects volunteered to participate in this trial and signed an informed consent form.

Exclusion Criteria:

Subjects with any of the following exclusion criteria were not eligible for enrollment in this trial:

1. Those with a history of epilepsy or other central nervous system disorders;
2. Those with a history of prolonged QT period or severe cardiac disease;
3. Women who are pregnant or breastfeeding (the safety of this therapy for the unborn child is not known);
4. Those with uncontrolled active infection;
5. Active hepatitis B or hepatitis C virus infection;
6. Those who have previously used any gene therapy product;
7. Those with insufficient amplification (\<5-fold) in response to CD3/CD28 co-stimulatory signals;
8. Creatinine \> 2.5 mg/dl or ALT / AST \> 3 times the upper limit of the normal range or bilirubin \> 2.0 mg/dl;
9. Those who suffer from other uncontrolled medical conditions that, in the opinion of the investigator, make them unsuitable for enrollment;
10. HIV-infected persons;
11. Any condition that, in the opinion of the investigator, may increase the risk to the subject or interfere with the results of the test.

Primary outcomes:
measure: Complete molecular response (CMR) rate
timeFrame: Up to 1 month after CAR-T cells infusion
Secondary outcomes:
measure: Complete molecular response (CMR) rate
timeFrame: Up to 1 month after CAR-T cells infusion
measure: Leukemia-free survival (LFS)
timeFrame: Up to 2 years after CD19 CAR-T cells infusion
measure: Overall survival (OS)
timeFrame: Up to 2 years after CD19 CAR-T cells infusion
measure: cumulative incidence of relapse (CIR)
timeFrame: Up to 2 years after CD19 CAR-T cells infusion
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Through study completion, an average of 2 years
measure: Characterization of relapse
timeFrame: Through study completion, an average of 2 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
References: