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Phase I/II Study of Enhanced CD33 CAR T Cells in Subjects With Relapsed or Refractory Acute Myeloid Leukemia

Primary Purpose

Acute Myeloid Leukemia, Relapse Leukemia, Refractory Acute Myeloid Leukemia

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

chimeric antigen receptor T cell

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

1 Year - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Candidates with relapse or refractory CD33+ acute myeloid leukemia, who have progressed on after treatment with all standard therapies or intolerant of standard care, have limited prognosis with currently available therapies and had no available curative treatment options (such as HSCT or chemotherapy)
Male or female, aged 1-70 years
No serious allergic constitution
Eastern Cooperative Oncology Group (ECOG) performance status (Oken et al.,1982) score 0 to 2
Have life expectancy of at least 60 days based on investigator's judgement
CD33 positive in bone marrow or cerebrospinal fluid (CSF) by flow cytometry, or CD33 positive in tumor tissues by immunohistochemistry; (CD33 positive criteria: Flow cytometry: Positive: > 80% of tumor cells expressed CD33 and the MFI of CD33 is the same as that in normal myeloid cells; Dim: > 80% of tumor cells expressed CD33, but the MFI of CD33 is lower than that in normal myeloid cells as least as 1log; Partial positive: 20-80% of tumor cells expressed CD33 and the MFI of CD33 is the same as that in normal myeloid cells. Tumor tissue immunohistochemistry: Positive > 30% tumor cells expressed CD33);
Provide a signed informed consent before any screening procedure; subjects who voluntarily participate in the study should have the ability to understand and sign the informed consent form and be willing to follow the study visit schedule and relevant study procedure, as specified in the protocol. Candidates aged 19-70 years need to be sufficiently conscious and able to sign the treatment consent form and voluntary consent form. Pediatric patients aged 1-7 years could be recruited after signing an informed consent form by a legal surrogate (Guardian); pediatric patients aged 8-18 years need to be sufficiently conscious and voluntarily signed an informed consent form, and their legal surrogates (guardians) were also required to sign a written informed consent form.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

Intracranial hypertension or disorder of consciousness
Symptomatic heart failure or severe arrhythmia
Symptoms of severe respiratory failure
Complicated with other types of malignant tumors
Diffuse intravascular coagulation
Serum creatinine and / or blood urea nitrogen ≥ 1.5 times of the normal value
Suffering from septicemia or other uncontrollable infections
Patients with uncontrollable diabetes
Severe mental disorders
Obvious and active intracranial lesions were detected by cranial magnetic resonance imaging (MRI)
Have received organ transplantation (excluding hematopoietic stem cell transplantation);
Reproductive-aged female patients with positive blood HCG test
Screened to be positive of infection of hepatitis (including hepatitis B and C), AIDS or syphilis
Patients with tumor burden higher than 30% requiring reinfusion of autologous CAR-T cells.

Sites / Locations

Beijing Boren HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

chimeric antigen receptor T cell treatment

Arm Description

Outcomes

Primary Outcome Measures

Incidence and type of dose-limiting toxicity (DLT)

Incidence and severity of adverse events (AE)

Secondary Outcome Measures

CR (complete remission) rate and CRi (complete remission with incomplete blood count recovery) rate to the CAR-T treatment

CR rate and CRi rate to the CAR-T treatment

Full Information

NCT ID

NCT04835519

First Posted

April 5, 2021

Last Updated

February 6, 2023

Sponsor

Beijing Boren Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04835519

Brief Title

Phase I/II Study of Enhanced CD33 CAR T Cells in Subjects With Relapsed or Refractory Acute Myeloid Leukemia

Official Title

Open-Label, Nonramdominzed, Single-Arm Phase I/II Study to Evaluate the Safety and Tolerability of Functionally Enhanced CD33 CAR T Cells in Subjects With Relapsed or Refractory Acute Myeloid Leukemia

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 8, 2021 (Actual)

Primary Completion Date

September 8, 2024 (Anticipated)

Study Completion Date

September 8, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Beijing Boren Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This is a open-label, nonramdominzed, single-arm, Phase I/II Study to evaluate safety and tolerability of functionally enhanced CD33 CAR-T cells in subjects with relapsed or refractory acute myeloid leukemia. 25 subjects will be enrolled. Subjects will be pretreated with chemotherapy prior to infusion of CAR T cells: about 5 days before cells transfusion, the patients who planned to reinfuse CAR T cells were treated with fluorodarabine 30 mg/m^2( body surface area) and cyclophosphamide 250 mg/m^2( body surface area) for 3 days. Then the Bayesian optimal interval phase I/II (Boin12) trial design will be used in this study: The protocol preset 2 dose levels: Dose 1 (DL-1) was 5×10^5 (±20%) CAR T cells/kg, and dose 2 (DL-2) was 1×10^6 (±20%) CAR T cells/kg. Phase I was the dose exploration phase. After determining the optimal biological dose (OBD), phase II will be expanded at the OBD dose by 10 cases, enrollment will reach 25 cases, and the trial will be discontinued. Moreover, the first 3 enrolled subjects per dose group will be on one by one dosing regimen. The expected initial dose of 5×10^5 (±20%) CAR T cells/kg could not be achieved due to preparation problems and should be placed in the reduced dose group. The number of cells will be collected by the above regimen as far as possible. If this is not possible, subjects can still enter the study upon investigator consideration but require documentation of dosing. The lowest dose is 1×10^5 CAR T cells/kg (±20%), and the highest dose is 1×10^6 CAR T cells/kg (±20%). If the dose is out of the range mentioned above, entry into the trial will not be considered.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia, Relapse Leukemia, Refractory Acute Myeloid Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

chimeric antigen receptor T cell treatment

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

chimeric antigen receptor T cell

Intervention Description

Subjects will be pretreated with chemotherapy prior to infusion of CAR T cells: about 5 days before cells transfusion, the patients who planned to reinfuse CAR T cells were treated with fluorodarabine 30 mg/m^2( body surface area) and cyclophosphamide 250 mg/m^2( body surface area) for 3 days. Then this study will be using the Bayesian optimal interval phase I/II (Boin12) trial design. The protocol preset 2 dose levels: Dose 1 (DL-1) was 5×10^5 (±20%) CAR T cells/kg, and dose 2 (DL-2) was 1×10^6 (±20%) CAR T cells/kg. If the above dose cannot be met, subjects can still enter the study upon investigator consideration but require documentation of dosing. The lowest dose is 1×10^5 CAR T cells/kg (±20%), and the highest dose is 1×10^6 CAR T cells/kg (±20%). If the dose is out of the range mentioned above, entry into the trial will not be considered.

Primary Outcome Measure Information:

Title

Incidence and type of dose-limiting toxicity (DLT)

Time Frame

day 21 post intravenous CAR T cell infusion

Title

Incidence and severity of adverse events (AE)

Time Frame

day 28 post intravenous CAR T cell infusion

Secondary Outcome Measure Information:

Title

CR (complete remission) rate and CRi (complete remission with incomplete blood count recovery) rate to the CAR-T treatment

Time Frame

day 15 post intravenous CAR T cell infusion

Title

CR rate and CRi rate to the CAR-T treatment

Time Frame

day 28 post intravenous CAR T cell infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: In order to be eligible to participate in this study, an individual must meet all of the following criteria: Candidates with relapse or refractory CD33+ acute myeloid leukemia, who have progressed on after treatment with all standard therapies or intolerant of standard care, have limited prognosis with currently available therapies and had no available curative treatment options (such as HSCT or chemotherapy) Male or female, aged 1-70 years No serious allergic constitution Eastern Cooperative Oncology Group (ECOG) performance status (Oken et al.,1982) score 0 to 2 Have life expectancy of at least 60 days based on investigator's judgement CD33 positive in bone marrow or cerebrospinal fluid (CSF) by flow cytometry, or CD33 positive in tumor tissues by immunohistochemistry; (CD33 positive criteria: Flow cytometry: Positive: > 80% of tumor cells expressed CD33 and the MFI of CD33 is the same as that in normal myeloid cells; Dim: > 80% of tumor cells expressed CD33, but the MFI of CD33 is lower than that in normal myeloid cells as least as 1log; Partial positive: 20-80% of tumor cells expressed CD33 and the MFI of CD33 is the same as that in normal myeloid cells. Tumor tissue immunohistochemistry: Positive > 30% tumor cells expressed CD33); Provide a signed informed consent before any screening procedure; subjects who voluntarily participate in the study should have the ability to understand and sign the informed consent form and be willing to follow the study visit schedule and relevant study procedure, as specified in the protocol. Candidates aged 19-70 years need to be sufficiently conscious and able to sign the treatment consent form and voluntary consent form. Pediatric patients aged 1-7 years could be recruited after signing an informed consent form by a legal surrogate (Guardian); pediatric patients aged 8-18 years need to be sufficiently conscious and voluntarily signed an informed consent form, and their legal surrogates (guardians) were also required to sign a written informed consent form. Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study: Intracranial hypertension or disorder of consciousness Symptomatic heart failure or severe arrhythmia Symptoms of severe respiratory failure Complicated with other types of malignant tumors Diffuse intravascular coagulation Serum creatinine and / or blood urea nitrogen ≥ 1.5 times of the normal value Suffering from septicemia or other uncontrollable infections Patients with uncontrollable diabetes Severe mental disorders Obvious and active intracranial lesions were detected by cranial magnetic resonance imaging (MRI) Have received organ transplantation (excluding hematopoietic stem cell transplantation); Reproductive-aged female patients with positive blood HCG test Screened to be positive of infection of hepatitis (including hepatitis B and C), AIDS or syphilis Patients with tumor burden higher than 30% requiring reinfusion of autologous CAR-T cells.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jing Pan, MD/PhD

Phone

+8618911067969

panj@borenhospital.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jing Pan, MD/PhD

Organizational Affiliation

Beijing Boren Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Beijing Boren Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jing Pan, Master

Phone

+8618911067969

panj@borenhospital.com

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Phase I/II Study of Enhanced CD33 CAR T Cells in Subjects With Relapsed or Refractory Acute Myeloid Leukemia

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