Clinical trial NCT05445765: Anti-CD33 CAR-T Cells for the Treatment of Relapsed/Refractory CD33+ Acute Myeloid Leukemia
Official title: Anti-CD33 CAR-T Cells for the Treatment of Relapsed/Refractory CD33+ Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Relapsed and/or Refractory Acute Myeloid Leukemia
High Risk Hematologic Malignancies
Keywords: CD33
anti-CD33 CAR
leukemia
acute myeloid leukemia
hematologic malignancies
Lead sponsor: iCell Gene Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: iCar Bio Therapeutics
First posted: 2022-07-06
Enrollment: 10
Sex: ALL
Minimum age (years): 2
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Signed written informed consent; Patients volunteer to participate in the clinical trial;
2. Diagnosis is mainly based on the World Health Organization (WHO) 2008;
3. 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%;
4. Leukemic blast cells express CD33 (CD33 positive by flow cytometry or immunohistochemistry ≥70%);
5. The expected survival period is greater than 12 weeks;
6. ECOG score ≤2;
7. Age 2-60 years old;
8. HGB≥70g/L (can be transfused);
9. 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:

1. Patients declining to consent for treatment
2. Prior solid organ transplantation
3. 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;
4. History of severe pulmonary dysfunction diseases;
5. Severe infection or persistent infection cannot be effectively controlled;
6. Severe autoimmune disease or congenital immunodeficiency;
7. Active hepatitis;
8. Human immunodeficiency virus (HIV) infection;
9. Clinically significant viral infections, or uncontrollable viral reactivation, including EBV (Epstein-Barr virus).

Primary outcomes:
measure: The number and incidence of adverse events after anti-CD33 CAR infusion.
timeFrame: 1 year, particularly the first 3 months after CAR infusion
Secondary outcomes:
measure: The disease response to anti-CD33 CAR T cells
timeFrame: 4 weeks
measure: Allogeneic hematopoietic stem cell transplantation (HCT)
timeFrame: 42 days after HCT ingraftment
measure: HCT 100% chymerism time
timeFrame: 2 weeks after HCT
measure: Overall survival
timeFrame: 1 year after HCT
measure: Progress-free survival
timeFrame: one year after HCT
measure: Treatment-related mortality
timeFrame: one year after HCT
Other outcomes:
Locations:
city: Langfang
country: China
facility: Hebei Yanda Lu Daopei Hospital
state: Hebei
Study officials:
affiliation: Hebei Yanda Lu Daopei Hospital
name: Peihua Lu, MD
role: PRINCIPAL_INVESTIGATOR
References: