CD22/CD19 CAR-T and Auto-HSCT Sandwich Strategy as Consolidation Therapy for B-ALL
Study Details
Study Description
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. We 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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) 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. Patients were followed up and minimal residual diseases (MRD) was monitored by flow cytometry and second-generation gene sequencing of IgH rearrangement.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CD22/CD19 CAR T and auto-HSCT sandwich strategy as consolidation therapy for B-ALL
|
Combination Product: CD22/CD19 CAR T and auto-HSCT "sandwich" strategy
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) 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. Patients were followed up and minimal residual diseases (MRD) was monitored by flow cytometry and second-generation gene sequencing of IgH rearrangement.
|
Outcome Measures
Primary Outcome Measures
- Number of adverse events [2 years]
Adverse events are evaluated with CTCAE V5.0 from the date of entry into this trial.
- Overall response rate (ORR） [1 month after auto-HSCT]
The percentage of participants achieving CR or CRi after the whole treatment strategy; patients not known to have any of these events are censored on the date they were last examined.
Secondary Outcome Measures
- Overall survival（OS） [2 years]
It is measured from the date of entry into this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.
- leukemia free survival（LFS） [2 years]
It is measured from the date of achievement of a remission until the date of relapse from CR, or CRi, or death from any cause; patients not known to have any of these events are censored on the date they were last examined.
Eligibility Criteria
Criteria
Inclusion Criteria:
- (1) 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; (2) positive expression of CD19 and CD22 in peripheral blood or bone marrow primary cells detected by flow cytometry; (3) 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; (4) subjects aged 18-65 years (including 18 and 65 years), regardless of gender; (5) T-cell amplification test pass; (6) expected survival > 3 months.
Exclusion Criteria:
- (1) patients with recurrence of only isolated extramedullary lesions; (2) combination of other malignant tumors; (3) previously treated with anti-CD19 or/and CD22 or/and CD3 therapies; (4) immunosuppressants use within 2 weeks prior to signing informed consent or plan to immunosuppressants after signing informed consent; (5) uncontrolled active infections; (6) HIV infection; (7) active hepatitis B or hepatitis C infection; (8) history of severe tachyphylaxis to aminoglycoside antibiotics; and (9) 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Affiliated Hospital of Soochow University | Suzhou | Jiangsu | China | 215006 |
Sponsors and Collaborators
- The First Affiliated Hospital of Soochow University
- National Natural Science Foundation of China(Grant No. 81970138)
- Jiangsu Province Natural Science Foundation of China (Grant No. BK20210091)
- Jining Medical University
- The Second People's Hospital of Huai'an
- First Affiliated Hospital Bengbu Medical College
- Northern Jiangsu Province People's Hospital
- Affiliated Hospital of Nantong University
- Suzhou Hospital of Traditional Chinese Medicine
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SZCART02