Anti-CD33 CAR-T Cells for the Treatment of Relapsed/Refractory CD33+ Acute Myeloid Leukemia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Anti-CD33 CAR-T Cells for the Treatment of Relapsed/Refractory CD33+ Acute Myeloid Leukemia

Conditions
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Relapsed and/or Refractory Acute Myeloid Leukemia, High Risk Hematologic Malignancies

Intervention / Treatment
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* Biological: anti-CD33 CAR T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent; Patients volunteer to participate in the clinical trial; Diagnosis is mainly based on the World Health Organization (WHO) 2008; 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%; Leukemic blast cells express CD33 (CD33 positive by flow cytometry or immunohistochemistry ≥70%); The expected survival period is greater than 12 weeks; ECOG score ≤2; Age 2-60 years old; HGB≥70g/L (can be transfused); 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: Patients declining to consent for treatment Prior solid organ transplantation 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; History of severe pulmonary dysfunction diseases; Severe infection or persistent infection cannot be effectively controlled; Severe autoimmune disease or congenital immunodeficiency; Active hepatitis; Human immunodeficiency virus (HIV) infection; Clinically significant viral infections, or uncontrollable viral reactivation, including EBV (Epstein-Barr virus).

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 60 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anti-CD33 CAR T cells<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number and incidence of adverse events after anti-CD33 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 | 1 year, particularly the first 3 months after CAR infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The disease response to anti-CD33 CAR T cells | 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). | 4 weeks | 
| Allogeneic hematopoietic stem cell transplantation (HCT) | 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. | 42 days after HCT ingraftment | 
| HCT 100% chymerism time | HCT 100% chymerism time | 2 weeks after HCT | 
| Overall survival | The time from the start of anti-CD33 CAR T injection to death is determined as the overall survival | 1 year after HCT | 
| Progress-free survival | 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. | one year after HCT | 
| Treatment-related mortality | Treatment-related mortality calculated from one year after HCT. | one year after HCT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD33, anti-CD33 CAR, leukemia, acute myeloid leukemia, hematologic malignancies