CD19/CD22 Bispecific CAR-T Cell Therapy for Relapsed/Refractory B-cell Lymphoma or Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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CAR-T cell therapy targeting CD19 has been shown to be effective in heavily-pretreated B-cell ALL or NHL, but relapses post-CAR-T are common, and CD19 antigen loss is one of the reasons. Thus, we supposed that CD19/CD22 bispecific CAR-T cell therapy would be more effective and less relapses would occur in B-ALL or NHL. In this prospective phase 2 clinical trial, we aim to explore the efficacy and safety of CD19/CD22 bispecific CAR-T cell therapy in relapsed/refractory B-ALL or Large B cell lymphoma.

Official Title
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CD19/CD22 Bispecific CAR-T Cell Therapy for Relapsed/Refractory B-cell Lymphoma or Acute Lymphoblastic Leukemia: a Prospective, Single-arm, Single-center, Phase 2 Clinical Trial

Conditions
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B-cell Acute Lymphoblastic Leukemia, B-cell Lymphoma, Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Drug: CD19/CD22-bispecific CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 14 years to 85 years, expected survival > 3 months; CD19/CD22 positive B-cell lymphoma or B-ALL; relapsed or refractory to standard first-line treatment; ECOG-PS score=0-2; Having at least one measurable lesions; Cardiac function: 1-2 levels; Liver: TBIL≤3ULN，AST ≤2.5ULN，ALT ≤2.5ULN; kidney: Cr≤1.25ULN; bone marrow: WBC ≥ 3.0×10e9/L, Hb ≥80 g/L, PLT ≥ 50×10e9/L; No serious allergic constitution; No other serious diseases that conflicts with the clinical program; No other cancer history; No serious mental disorder; Informed consent is signed by a subject or his lineal relation. Exclusion Criteria: Pregnant or lactating women; (female participants of reproductive potential must have a negative serum or urine pregnancy test); Uncontrolled active infection, HIV infection, syphilis serology reaction positive; Active hepatitis B or hepatitis C infection; Recent or current use of glucocorticoid or other immunosuppressor; With severe cardiac, liver, renal insufficiency, diabetes and other diseases; Participate in other clinical research in the past three months; previously treatment with any gene therapy products; Researchers think of that does not fit to participate in the study, or other cases that affect the clinical trial results.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD19/CD22 CAR-T group<br>Patients would receive autologous CAR-T cell therapy targeting both CD19 and CD22. The dosage for CD19-CAR-T cell was 2×10e6/kg and CD22-CAR-T cell was 1×10e6/kg. Both CAR-T cells were infused at the same day. | Drug: CD19/CD22-bispecific CAR-T cells<br>* CD19/CD22-bispecific CAR-T cells were infused at the same day with 2×10e6/kg and 1×10e6/kg dosage, respectively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best ORR | Overall response rate means sum of complete response rate and partial response rate | From the day of CAR-T cells infusion to 3 months post-CAR-T cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best CR rate | CR was defined as complete remission evaluated using PET-CT scan or BM test | From the day of CAR-T cells infusion to 3 months post-CAR-T cells infusion | 
| Progression free survival (PFS) | PFS was defined from the date of CAR-T infusion to the date fo confirmed disease progression or death of any reason | From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion | 
| overall survival (OS) | OS was defined from the date of CAR-T infusion to the date fo death | From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion |