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

Primary Purpose

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

Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
anti-CD33 CAR T cells
Sponsored by
iCell Gene Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed and/or Refractory Acute Myeloid Leukemia focused on measuring CD33, anti-CD33 CAR, leukemia, acute myeloid leukemia, hematologic malignancies

Eligibility Criteria

2 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Hebei Yanda Lu Daopei Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

anti-CD33 CAR T cells

Arm Description

Dose escalation phase: anti-CD33 CAR T cells will be transduced with a lentiviral vector to express anti-CD33 CARs

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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).
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.
HCT 100% chymerism time
HCT 100% chymerism time
Overall survival
The time from the start of anti-CD33 CAR T injection to death is determined as the overall survival
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.
Treatment-related mortality
Treatment-related mortality calculated from one year after HCT.

Full Information

First Posted
June 30, 2022
Last Updated
June 30, 2022
Sponsor
iCell Gene Therapeutics
Collaborators
iCar Bio Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT05445765
Brief Title
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

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 1, 2022 (Anticipated)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
iCell Gene Therapeutics
Collaborators
iCar Bio Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed and/or Refractory Acute Myeloid Leukemia, High Risk Hematologic Malignancies
Keywords
CD33, anti-CD33 CAR, leukemia, acute myeloid leukemia, hematologic malignancies

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
anti-CD33 CAR T cells
Arm Type
Experimental
Arm Description
Dose escalation phase: anti-CD33 CAR T cells will be transduced with a lentiviral vector to express anti-CD33 CARs
Intervention Type
Biological
Intervention Name(s)
anti-CD33 CAR T cells
Intervention Description
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.
Primary Outcome Measure Information:
Title
The number and incidence of adverse events after anti-CD33 CAR infusion.
Description
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
Time Frame
1 year, particularly the first 3 months after CAR infusion
Secondary Outcome Measure Information:
Title
The disease response to anti-CD33 CAR T cells
Description
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).
Time Frame
4 weeks
Title
Allogeneic hematopoietic stem cell transplantation (HCT)
Description
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.
Time Frame
42 days after HCT ingraftment
Title
HCT 100% chymerism time
Description
HCT 100% chymerism time
Time Frame
2 weeks after HCT
Title
Overall survival
Description
The time from the start of anti-CD33 CAR T injection to death is determined as the overall survival
Time Frame
1 year after HCT
Title
Progress-free survival
Description
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.
Time Frame
one year after HCT
Title
Treatment-related mortality
Description
Treatment-related mortality calculated from one year after HCT.
Time Frame
one year after HCT

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kevin Pinz, MS
Phone
6315386218
Email
kevin.pinz@icellgene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peihua Lu, MD
Organizational Affiliation
Hebei Yanda Lu Daopei Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hebei Yanda Lu Daopei Hospital
City
Langfang
State/Province
Hebei
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peihua Lu, MD
Phone
011-86-18611636171
Email
peihua_lu@126.com

12. IPD Sharing Statement

Learn more about this trial

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

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