A Feasibility and Safety Study of Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cell Immunotherapy for Relapsed or Refractory Leukemia and Lymphoma
Study Details
Study Description
Brief Summary
CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory B-cell malignancies; however, a subset of patients relapse due to the loss of CD19 in tumor cells. Dual Specificity CD19 and CD20 or CD22 CAR-T cells can recognize and kill the CD19 negative malignant cells through recognition of CD20 or CD22. This is a phase 1/2 study designed to determine the safety of the allogenic gene-edited dual specificity CD19 and CD20 or CD22 CAR-T cells and the feasibility of making enough to treat patients with relapsed or refractory hematological malignancies.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
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PRIMARY OBJECTIVES:
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To evaluate the feasibility and safety of universal dual specificity CD19 and CD20 or CD22 CAR-T cells in patients with relapsed or refractory leukemia and lymphoma.
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To evaluate the duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells. Real Time polymerase chain receptor (RT-PCR) and Flow cytometry(FCM) analysis of PB,BM and lymph node will be used to detect and quantify survival of universal dual specificity CD19 and CD20 or CD22 CAR-T cells over time.
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SECONDARY OBJECTIVES:
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For patients with detectable disease, measure anti-tumor response due to universal dual specificity CD19 and CD20 or CD22 CAR-T cell infusions.
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Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable universal dual specificity CD19 and CD20 or CD22 CAR-T cells (loss of engraftment).
The CAR-T cells will be administered by i.v. injection over 20-30 minutes as a using a "split dose" approach to dosing: 10% on day 0, 30% on day 1 and 60% on day 2.
Study Design
Outcome Measures
Primary Outcome Measures
- Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability [24 weeks]
- MTD of universal dual specificity CD19 and CD20 or CD22 CAR-T cells [4 weeks]
The highest dose of universal dual specificity CD19 and CD20 or CD22 CAR-T cells that is estimated to result in defined Dose Limiting Toxicity (DLT) with the exception of allowable 'expected' AEs associated with the intravenous infusion of universal dual s
- Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes [24 weeks]
Secondary Outcome Measures
- Six-month Objective response rate of complete remission and partial remission [24 weeks]
- Six-month Overall survival [24 weeks]
- Six-month Progression free survival [24 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female participant
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12 Years to 70 Years (Child, Adult, Senior)
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Patient with relapsed or refractory B-cell leukemia or lymphoma
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Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
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Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
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Adequate organ function
Exclusion Criteria:
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Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
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Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
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Richter's syndrome
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Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
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Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
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Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible
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Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
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Patient has an investigational medicinal product within the last 30 days prior to screening
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Previous treatment with investigational gene or cell therapy medicine products
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Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
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Pregnant or nursing women
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital | Beijing | Beijing | China | 100853 |
Sponsors and Collaborators
- Chinese PLA General Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CHN-PLAGH-BT-026