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

June 20, 2024 updated by: Beijing Boren Hospital

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
5

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100000
        • Beijing Boren Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

  1. 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)
  2. Male or female, aged 1-70 years
  3. No serious allergic constitution
  4. Eastern Cooperative Oncology Group (ECOG) performance status (Oken et al.,1982) score 0 to 2
  5. Have life expectancy of at least 60 days based on investigator's judgement
  6. 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);
  7. 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:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: chimeric antigen receptor T cell treatment
Biological: chimeric antigen receptor T cell
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Incidence and type of dose-limiting toxicity (DLT)
Time Frame: day 21 post intravenous CAR T cell infusion
day 21 post intravenous CAR T cell infusion
Incidence and severity of adverse events (AE)
Time Frame: day 28 post intravenous CAR T cell infusion
day 28 post intravenous CAR T cell infusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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
day 15 post intravenous CAR T cell infusion
CR rate and CRi rate to the CAR-T treatment
Time Frame: day 28 post intravenous CAR T cell infusion
day 28 post intravenous CAR T cell infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Beijing Boren Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jing Pan, MD/PhD, Beijing Boren Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 8, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 19, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 19, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 5, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 5, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 8, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 21, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BRYY-IIT-LCYJ-2021-003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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