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

High Risk Hematologic Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05445765
• Other study ID #: ICG165-001
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: July 1, 2022
• Est. completion date: June 30, 2024

Study information

• Verified date: June 2022
• Source: iCell Gene Therapeutics
• Contact: Kevin Pinz, MS
• Phone: 6315386218
• Email: kevin.pinz[@]icellgene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 60 Years

Eligibility

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).

Related Conditions & MeSH terms

• Hematologic Neoplasms
• High Risk Hematologic Malignancies
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Neoplasms

Intervention

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.

Locations

Country	Name	City	State
China	Hebei Yanda Lu Daopei Hospital	Langfang	Hebei

Sponsors (2)

Lead Sponsor	Collaborator
iCell Gene Therapeutics	iCar Bio Therapeutics

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	HCT 100% chymerism time	HCT 100% chymerism time	2 weeks after HCT
Secondary	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
Secondary	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
Secondary	Treatment-related mortality	Treatment-related mortality calculated from one year after HCT.	one year after HCT