Safety and Efficacy Study of CI-135 CAR-T Cells in Subjects with Relapsed or Refractory Acute Myeloid Leukemia

November 12, 2024 updated by: Beijing Boren Hospital

First-in-Human (FIH), Open-Label, Non-Randomized, Single-Arm Phase 1 Study to Evaluate the Safety and Efficacy of CI-135 CAR-T Cells in Subjects with Relapsed or Refractory Acute Myeloid Leukemia

This is a FIH, single center, open label, non-randomized, single-arm, Phase I clinical trial to evaluate the safety and efficacy of CI-135 CAR-T cells in subjects with relapsed or refractory Acute Lymphoblastic Leukemia. This study is a dose-escalation study that includes 2 dose levels, and a total of 4-7 subjects will be enrolled. CI-135 CAR-T cells will be manufactured using PBMC collected from the subjects, and will be infused intravenously into subjects after lymphodepletion.

Study Overview

Status

Status

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Withdrawn

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

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 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, 100070
        • Beijing Gaobo 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

5 years to 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥5 years old and ≤70 years old, male or female;
  2. Expected survival exceeds 12 weeks;
  3. Diagnosed as primary or secondary AML patients that meet the World Health Organization (WHO) classification, and meet any of the following conditions: a) AML patients who have not reached complete remission after at least 3 cycles of standard induction chemotherapy B) AML patients who have achieved complete remission after induction chemotherapy and relapse within 1 year; c) AML patients who have relapsed after achieving complete remission after induction chemotherapy for more than 1 year and have not remitted after 1 course of induction chemotherapy; d) AML patients who have relapsed after transplantation ; E) AML patients who have experienced 2 or more relapses. For patients who meet one of a), b), and c) and have FLT-3 mutations, in addition to induction therapy, they should also receive at least one TKI treatment and has not achieved complete remission or relapsed after complete remission (except patients who cannot tolerate TKI treatment or have contraindications to TKI treatment).
  4. The FLT-3 mutation is positive by the leukemia cell gene detection, or the FLT-3 expression is ≥35%;
  5. ECOG score 1-2;

  6. Liver, kidney, heart and lung functions meet the following requirements:

    1. Glomerular filtration rate ≥60 ml/min/1.73 m2 or serum creatinine ≤2 times the upper limit of normal;
    2. Serum AST, ALT≤3 times the upper limit of normal, and total bilirubin≤1.5 times the upper limit of normal;
    3. Blood oxygen saturation> 92%;
    4. The ventricular ejection fraction ≥50%, there is no pericardial effusion detected by ultrasound, and no clinically significant ECG changes.
  7. Able to understand this experiment and sign the informed consent form.

Exclusion Criteria:

  1. Diagnosed as acute promyelocytic leukemia (APL M3);
  2. Accompanied with other uncontrolled malignant tumors (except those that would not interfere with the safety or efficacy evaluation of the trial).
  3. Have received CAR-T cell or other genetically modified cell therapy in the past;
  4. Medical history or evidence of significant cardiovascular risk, including any of the following conditions: congestive heart failure, unstable angina, clinically significant arrhythmia (such as ventricular fibrillation, ventricular tachycardia, etc.), performed coronary angioplasty 6 months before infusion, intracardiac defibrillator or any clinically-related complications that may pose a risk to the safety of the subject or interfere with the evaluation, procedures or completion of the research;
  5. Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and whose peripheral blood HBV DNA titer test is greater than or equal to the lower limit of detection; those who are positive for hepatitis C virus (HCV) antibody and positive for peripheral blood HCV RNA; Human immunodeficiency virus (HIV) antibody positive; syphilis test positive;
  6. Acute or chronic hepatitis C is positive. Exceptions: acute hepatitis C with complete clearance of the virus; chronic hepatitis C, with a sustained virological response 24 weeks after completion of hepatitis C treatment (SVR24) determined an undetectable viral load;
  7. A history of arterial or venous thrombosis within 3 months before enrollment;
  8. Any graft-versus-host disease that requires systemic application of immunomodulators;
  9. A history of central nervous system disease or subjects who need treatment (for example, uncontrolled seizures);
  10. Active infection that cannot be controlled.
  11. Subjects who are known to be allergic to the components of CI-135 CAR-T cells or any components of the lymphodepletion regimen (cyclophosphamide and fludarabine).
  12. Women who are pregnant or breastfeeding, and female patients who plan to become pregnant within 1 year after cell infusion, or male patients whose partners plan to become pregnant within 1 year after their infusion.
  13. Other situations that are considered to be unsuitable to participate in the study by researchers.

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: CI-135 CAR-T
chimeric antigen receptor T cell treatment
Biological: CI-135 CAR-T cells (0.5 x 10^6 CAR-T+ cells/kg，1.0 x 10^6 CAR-T+ cells/kg)
Recommended lymphodepletion regimen: cyclophosphamide (250 mg/m2/d, ×3d) and fludarabine (30 mg/m2/d, ×3d). If the patient has a hematological toxicity of grade 3 or higher, the alternative regimen is: cyclophosphamide (125mg/m2/d, ×3d) and fludarabine (15 mg/m2/d, ×3d). During lymphodepletion, physicians can give anti-myeloid drugs such as demethoxydaunorubicin or daunorubicin as appropriate.

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
Measure Description
Time Frame
Dose-limiting toxicity (DLT)
Time Frame: 28 days post intravenous infusion
Dose-limiting toxicity (DLT)
28 days post intravenous 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
Measure Description
Time Frame
Adverse events
Time Frame: until two years after cell infusion
Incidence and severity of adverse events as assessed by NCI-CTCAE 5.0
until two years after cell infusion
Concentration of PK CAR positive T cells in peripheral blood
Time Frame: until two years after cell infusion
PK CAR positive T cells in peripheral blood, PK CAR transgene levels in peripheral blood
until two years after cell infusion
Pharmacodynamic data in peripheral blood
Time Frame: until two years after cell infusion
Time profile of CAR positive T cells concentrations in peripheral blood
until two years after cell infusion
Objective response rate (ORR)
Time Frame: until two years after cell infusion
Objective response rate (ORR)
until two years after cell infusion
Duration of remission (DOR) after infusion
Time Frame: until two years after cell infusion
refers to the time from the first assessment of CR or PR to the first assessment of disease progression or death from any cause
until two years after cell infusion
Progression-free survival (PFS) after infusion
Time Frame: until two years after cell infusion
refers to the time from cell infusion to the first assessment of tumor progression or recurrence or death from any cause
until two years after cell infusion
Overall survival (OS) after infusion
Time Frame: until two years after cell infusion
efers to the time from cell infusion to death due to any cause. For subjects who have dropped out before death, the dates of their last visit would be counted as their time of death; if the subject receives other new treatments, the time of death will be calculated based on the start date of the new treatment; if the study ends, the time of death will be calculated based on the end date
until two years after cell infusion
Time of human anti-mouse antibody production persist in human body （Immunogenicity）
Time Frame: until two years after cell infusion
Immunogenicity will be analyzed during the study, including the time of human anti-mouse antibody production and how long will it last in the body.
until two years after 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 Gaobo 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.
December 13, 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.
December 12, 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.
December 12, 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).
December 29, 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.
February 23, 2022

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.
March 4, 2022

Study Record Updates

Last Update Posted (Estimated)

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.
November 14, 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.
November 12, 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.
August 1, 2024

More Information

Terms related to this study

Keywords

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-2021-018

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

product manufactured in and exported from the U.S.

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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