Back to resultsCD22/CD19 CAR-T and Auto-HSCT Sandwich Strategy as Consolidation Therapy for B-ALL
Primary Purpose
B-cell Acute Lymphoblastic Leukemia
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CD22/CD19 CAR T and auto-HSCT "sandwich" strategy
Sponsored by
About this trial
This is an interventional treatment trial for B-cell Acute Lymphoblastic Leukemia focused on measuring CD22/CD19 CAR-T, auto-HSCT
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.
Sites / Locations
- The First Affiliated Hospital of Soochow UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CD22/CD19 CAR T and auto-HSCT sandwich strategy as consolidation therapy for B-ALL
Arm Description
Outcomes
Primary Outcome Measures
Number of adverse events
Adverse events are evaluated with CTCAE V5.0 from the date of entry into this trial.
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT05470777
First Posted
July 20, 2022
Last Updated
October 30, 2022
Sponsor
The First Affiliated Hospital of Soochow University
Collaborators
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
1. Study Identification
Unique Protocol Identification Number
NCT05470777
Brief Title
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
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 19, 2020 (Actual)
Primary Completion Date
May 1, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital of Soochow University
Collaborators
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
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. 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. 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) 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Acute Lymphoblastic Leukemia
Keywords
CD22/CD19 CAR-T, auto-HSCT
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CD22/CD19 CAR T and auto-HSCT sandwich strategy as consolidation therapy for B-ALL
Arm Type
Experimental
Intervention Type
Combination Product
Intervention Name(s)
CD22/CD19 CAR T and auto-HSCT "sandwich" strategy
Intervention 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.
Primary Outcome Measure Information:
Title
Number of adverse events
Description
Adverse events are evaluated with CTCAE V5.0 from the date of entry into this trial.
Time Frame
2 years
Title
Overall response rate (ORR）
Description
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.
Time Frame
1 month after auto-HSCT
Secondary Outcome Measure Information:
Title
Overall survival（OS）
Description
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.
Time Frame
2 years
Title
leukemia free survival（LFS）
Description
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.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sheng-Li Xue, M.D.
Phone
+86 512 67781139
Email
slxue@suda.edu.cn
Facility Information:
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sheng-Li Xue, M.D.
Phone
+86 512 6778 1139
Email
slxue@suda.edu.cn
12. IPD Sharing Statement
Learn more about this trial
CD22/CD19 CAR-T and Auto-HSCT Sandwich Strategy as Consolidation Therapy for B-ALL
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