CD22/CD19 CAR-T and Auto-HSCT Sandwich Strategy as Consolidation Therapy for B-ALL

B-cell Acute Lymphoblastic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05470777
• Other study ID #: SZCART02
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 19, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: November 2023
• Source: The First Affiliated Hospital of Soochow University
• Contact: Sheng-Li Xue, M.D.
• Phone: +86 512 67781139
• Email: slxue[@]suda.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: December 31, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• B-cell Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (9)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University	Affiliated Hospital of Nantong University, First Affiliated Hospital Bengbu Medical College, Jiangsu Province Natural Science Foundation of China (Grant No. BK20210091), Jining Medical University, National Natural Science Foundation of China(Grant No. 81970138), Northern Jiangsu Province People's Hospital, Suzhou Hospital of Traditional Chinese Medicine, The Second People's Hospital of Huai'an

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of adverse events	Adverse events are evaluated with CTCAE V5.0 from the date of entry into this trial.	2 years
Primary	Overall response rate (ORR)	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.	1 month after auto-HSCT
Secondary	Overall survival(OS)	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.	2 years
Secondary	leukemia free survival(LFS)	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.	2 years