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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: High Risk Hematologic Malignancies; Relapsed and/or Refractory Acute Myeloid Leukemia
• Intervention / Treatment: Biological: anti-CD33 CAR T cells

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 Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hebei
    • Langfang, Hebei, China
      • Hebei Yanda Lu Daopei Hospital
      • Contact: Peihua Lu, MD; Phone Number: 011-86-18611636171; Email: peihua_lu@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 60 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: iCell Gene Therapeutics
• Collaborators: iCar Bio Therapeutics

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2022
• Primary Completion (ANTICIPATED): June 30, 2024
• Study Completion (ANTICIPATED): June 30, 2024

Study Registration Dates

• First Submitted: June 30, 2022
• First Submitted That Met QC Criteria: June 30, 2022
• First Posted (ACTUAL): July 6, 2022

Study Record Updates

• Last Update Posted (ACTUAL): July 6, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: acute myeloid leukemia; hematologic malignancies; leukemia; CD33; anti-CD33 CAR
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: ICG165-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No