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

Phase 1

• Conditions: High Risk Hematologic Malignancies; Relapsed and/or Refractory Acute Myeloid Leukemia
• Interventions: Biological: anti-CD33 CAR T cells

• Registration Number: NCT05445765
• Lead Sponsor: iCell Gene Therapeutics

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.

Study Timeline

• Status Verified: 2022-06
• Study First Submitted: 2022-06-30
• Study First Submitted QC: 2022-06-30
• Last Update Submitted: 2022-06-30
• Study Start: 2022-07-01
• Study First Posted: 2022-07-06
• Last Update Posted: 2022-07-06
• Primary Completion: 2024-06-30
• Study Completion: 2024-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
anti-CD33 CAR T cells	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
Treatment-related mortality	one year after HCT	Treatment-related mortality calculated from one year after HCT.
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.

Trial Locations

Locations (1)

Hebei Yanda Lu Daopei Hospital; 🇨🇳 Langfang, Hebei, China