Anti-CD33 CAR-T Cells for the Treatment of Relapsed/Refractory CD33+ Acute Myeloid Leukemia
Study Details
Study Description
Brief Summary
This is a phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of anti-CD33 CAR-T cells in patients with relapsed and/or refractory, high risk hematologic malignancies.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
AML is a rapidly progressing blood cancer and treated by high-dose multi-agent chemotherapy potentially followed by hematopoietic stem cell transplantation. Despite such intensive therapies, which are often associated with considerable toxicities and even death, about 60-70% of AML patients still relapse. Furthermore, the five-year survival rate from AML remains at a dismal 27%. AML is composed mostly of CD33+ leukemic blast cells. Therefore, CD33 is a potential good target by CAR T cells.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: anti-CD33 CAR T cells Dose escalation phase: anti-CD33 CAR T cells will be transduced with a lentiviral vector to express anti-CD33 CARs |
Biological: anti-CD33 CAR T cells
Anti-CD33 CAR T cells are used to treat patients. Patient will be administered either fresh or thawed CAR T cells by IV injection after receiving lymphodepleting chemotherapy.
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Outcome Measures
Primary Outcome Measures
- The number and incidence of adverse events after anti-CD33 CAR infusion. [1 year, particularly the first 3 months after CAR infusion]
Determine the toxicity profile of anti-CD33 CAR T cell therapy including the number, incidence, and severity of symptoms such as cytokine release syndromes and neurotoxicity
Secondary Outcome Measures
- The disease response to anti-CD33 CAR T cells [4 weeks]
The disease response to anti-CD33 CAR T cells is evaluated by bone marrow biopsy and aspirate at 1, 2, 3, and 4 weeks. The proportion of subjects receiving anti-CD33 CAR T infusion to 1) morphological remission (blasts <5%): 2) flow cytometry analysis was blast negative, and 3) molecular biological remission (if applicable).
- Allogeneic hematopoietic stem cell transplantation (HCT) [42 days after HCT ingraftment]
Allogeneic hematopoietic stem cell transplantation (HCT) is performed after anti-CD33 CAR T treatment. The time after HCT engraftment [time range: 42 days after HCT ingraftemnt] is calculated from the day of HCT until the absolute neutrophil count (ANC) is greater than 500 / ul for three consecutive days.
- HCT 100% chymerism time [2 weeks after HCT]
HCT 100% chymerism time
- Overall survival [1 year after HCT]
The time from the start of anti-CD33 CAR T injection to death is determined as the overall survival
- Progress-free survival [one year after HCT]
Progress-free survival is measured from the injection of anti-CD33 CAR T cells until the record of disease progression or death due to any reason, whichever comes first.
- Treatment-related mortality [one year after HCT]
Treatment-related mortality calculated from one year after HCT.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Signed written informed consent; Patients volunteer to participate in the clinical trial;
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Diagnosis is mainly based on the World Health Organization (WHO) 2008;
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Complete remission cannot be achieved after induction therapy; recurrence occurs after completion remission; the burden of leukemic blasts in the peripheral blood or bone marrow is greater than 5%;
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Leukemic blast cells express CD33 (CD33 positive by flow cytometry or immunohistochemistry ≥70%);
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The expected survival period is greater than 12 weeks;
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ECOG score ≤2;
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Age 2-60 years old;
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HGB≥70g/L (can be transfused);
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Total bilirubin does not exceed 3 times the upper limit of normal value, and AST and ALT do not exceed 5 times the upper limit of normal value.
Exclusion Criteria:
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Patients declining to consent for treatment
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Prior solid organ transplantation
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One of the following cardiac issues: atrial fibrillation; myocardial infarction within the past 12 months; prolonged QT syndrome or secondary QT prolongation; clinically significant pericardial effusion; cardiac insufficiency NYHA (New York Heart Association) III or IV;
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History of severe pulmonary dysfunction diseases;
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Severe infection or persistent infection cannot be effectively controlled;
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Severe autoimmune disease or congenital immunodeficiency;
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Active hepatitis;
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Human immunodeficiency virus (HIV) infection;
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Clinically significant viral infections, or uncontrollable viral reactivation, including EBV (Epstein-Barr virus).
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Hebei Yanda Lu Daopei Hospital | Langfang | Hebei | China |
Sponsors and Collaborators
- iCell Gene Therapeutics
- iCar Bio Therapeutics
Investigators
- Principal Investigator: Peihua Lu, MD, Hebei Yanda Lu Daopei Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ICG165-001