Clinical trial NCT05470777: CD22/CD19 CAR-T and Auto-HSCT Sandwich Strategy as Consolidation Therapy for B-ALL
Official title: Safety and Efficacy of CD22/CD19 CAR T-cells and Autologous HSCT Sandwich Strategy as Consolidation Therapy for B-cell Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: B-cell Acute Lymphoblastic Leukemia
Keywords: CD22/CD19 CAR-T
auto-HSCT
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
Collaborators: name: National Natural Science Foundation of China(Grant No. 81970138)
name: Jiangsu Province Natural Science Foundation of China (Grant No. BK20210091)
name: Jining Medical University
name: The Second People's Hospital of Huai'an
name: The First Affiliated Hospital of Bengbu Medical University
name: Northern Jiangsu People's Hospital
name: Affiliated Hospital of Nantong University
name: Suzhou Hospital of Traditional Chinese Medicine
First posted: 2022-07-22
Enrollment: 37
Sex: ALL
Minimum age (years): 15
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Chimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable efficacy in B-cell acute lymphoblastic leukemia (B-ALL). However, relapse after CAR-T has been a major issue. Multi-antigen CAR T and combination with other regimens may reduce the relapse rate. The investigators first conducted CD22/CD19 CAR T-cells and auto-HSCT "sandwich " strategy as consolidation therapy in patients with B-ALL. The main Purpose of this study was to observe the safety and efficacy of this new strategy.

Detailed description: The patients received sequential infusion of CD22 and CD19 CAR-T cells (co-stimulatory molecule was 4-1BB and infusion dose was 5\*10\^6/kg respectively,CAR-T1) after standard induction and consolidation chemotherapy. Autologous stem cells mobilization and collection were performed 6-8 weeks after CAR-T infusion. Standard BuCy as conditioning regimen for Auto-HSCT was used 4 weeks after successful stem cell collection. CD22 and CD19 CAR-T cells were re-infused 2 days after Auto-HSCT(CAR-T2). Patients were followed up and minimal residual diseases (MRD) was monitored by flow cytometry and second-generation gene sequencing of IgH rearrangement.

Eligibility criteria: Inclusion Criteria:

* subjects with a primary diagnosis of B-ALL who have any of the following: (a) no suitable allogeneic HSCT donor. (b) refusal of allogeneic HSCT.
* positive expression of CD19 and CD22 in peripheral blood or bone marrow primary cells detected by flow cytometry.
* cardiac ultrasound left ventricular ejection fraction ≥ 50%; Creatinine ≤ 1.6 mg/dl; alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the normal range and total bilirubin ≤ 2.0 mg/dl; Pulmonary function ≤ grade 1 dyspnea (CTCAE v5.0) with oxygen saturation \> 91% without oxygenation.
* subjects aged 15-65 years (including 15 and 65 years), regardless of gender.
* T-cell amplification test pass.
* expected survival \> 3 months.

Exclusion Criteria:

* patients with recurrence of only isolated extramedullary lesions.
* combination of other malignant tumors.
* previously treated with anti-CD19 or/and CD22 or/and CD3 therapies.
* immunosuppressants use within 2 weeks prior to signing informed consent or plan to immunosuppressants after signing informed consent.
* uncontrolled active infections.
* HIV infection.
* active hepatitis B or hepatitis C infection.
* history of severe tachyphylaxis to aminoglycoside antibiotics.
* history or presence of clinically relevant Central Nervous System (CNS) pathology, such as epilepsy, generalized seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.

Primary outcomes:
measure: Overall survival (OS)
timeFrame: 2 years
Secondary outcomes:
measure: Leukemia-free survival (LFS)
timeFrame: 2 years
measure: Measurable residual disease (MRD) negative rate and duration
timeFrame: 2 years
measure: Incidence of adverse events (AEs)
timeFrame: 2 years
Other outcomes:
measure: Difference in 2-year LFS between the sandwich strategy treatment and external allo-HSCT control group
timeFrame: 2 years
measure: Difference in 2-year OS between the sandwich strategy treatment and external allo-HSCT control group
timeFrame: 2 years
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
References: