Anti-CD7 CAR-Engineered T Cells for T Lymphoid Malignancies Malignancies

March 1, 2022 updated by: MEI HENG, Wuhan Union Hospital, China

Safety and Efficacy of Anti-CD7 CAR-Engineered T Cells for Relapsed/Refractory T Lymphoid Malignancies: a Single-center, Open-label, Non-randomized, Single-arm Clinical Study

This is a single-center, open-label, single-arm study to evaluate the primary safety and efficacy of anti-CD7 chimeric antigen receptor(CAR)-modified T cells(CAR7-Ts) in patients with relapsed or refractory T lymphoid malignancies.

Study Overview

Status

Status

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

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.

Detailed Description

Chimeric antigen receptor-T cells (CAR-T) have made breakthroughs in the treatment of B-cell tumors, especially refractory/relapsed acute B lymphocytes. CD7 is a transmembrane glycoprotein expressed by T cells and natural killer cells and their precursors; it is also expressed in >95% of lymphoblastic T-cell leukemias and lymphomas . CD7 was previously evaluated as a target for immunotoxin-loaded antibodies in patients with T-cell malignancies, but tumor responses were limited.

Enhancing the potency of CD7-directed cytotoxicity by substituting donor-derived CAR-T cells for a monoclonal antibody would augment the efficacy of CD7-targeted therapy in patients with T-cell malignancies. To prepare CAR7-T cells, CD7 expression is suppressed on donor-derived T cells by unique blocking technique, and CD7-negative T cells are transduced with a humanized anti-CD7-41BB-CD3ζ lentiviral vector.

This is an investigational study. The objectives are to evaluate the safety and efficacy of CAR7-T cells in patients with CD7+ T-cell malignancies.

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 (Anticipated)

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.
24

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
    • Hubei
      • Wuhan, Hubei, China, 430022
        • Recruiting
        • Union Hospital, Huazhong University of Science and Technology
        • Contact:
        • Principal Investigator:
          • Heng Mei, M.D., Ph.D

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

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

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Aged from 14 to 70 years;
  2. Expected survival over 60 days;
  3. Eastern Cooperative Oncology Group score 0-2;
  4. Diagnosed as T-cell hematologic malignancies (including leukemia and lymphoma) according to WHO2016 criteria;
  5. Patients must relapse or be refractory after at least two lines of therapy.

  6. CD7 were positive in bone marrow or cerebrospinal fluid by immunohistochemistry or flow cytometry at screening, and one of the following conditions is satisfied:

    A. No remission was achieved after at least 2 lines of standard therapy; B. Relapse or progression after standard treatment; C. Relapse after autologous or allogeneic hematopoietic stem cell transplantation;

  7. Have no fertility requirements or plans for one year since enrollment in this clinical trial;
  8. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.

Exclusion Criteria:

  1. Complicated with central system leukemia/lymphoma with active intracranial lesions;
  2. Existing or preexisting CNS conditions, such as epileptic seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS related autoimmune disease;
  3. Symptomatic heart failure or severe arrhythmias;
  4. Symptoms of severe respiratory failure;
  5. Complicated with other types of malignant tumors;
  6. Serum creatinine and/or urea nitrogen ≥ 1.5 times of normal value;
  7. Suffer from sepsis or other uncontrollable infections;
  8. Intracranial hypertension or brain consciousness disorder;
  9. Severe mental disorders;
  10. Have received organ transplantation (excluding bone marrow transplantation);
  11. Female patients (fertile patients) had positive blood HCG test;
  12. Hepatitis (including hepatitis B and C), AIDS and syphilis were screened positive;
  13. Patients with graft-versus-host disease (GVHD) or who require immunosuppressant treatment;
  14. The absolute value of lymphocytes was too low to manufacture CART cells;
  15. Other conditions considered inappropriate by the researcher.

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: Fludarabine + Cyclophosphamide + anti-CD7 CAR-T Cells
Patients will received lymphodepletion with fludarabine (30 mg/kg) and cyclophosphamide (250 mg/kg) on day -5, -4, and -3, followed by the infusion of CAR7-T cells with the dose of 1×10^6/kg and 2×10^6/kg (with an allowance of ±20%). If no dose-limited toxicity (DLT) emerges in the group, then the subsequent higher dose will be used in the next group. If DLT emerges in a single subject in any dose level, 3 more subjects will be enrolled to the same dose level. The maximum dose could be extended.
Drug: Fludarabine + Cyclophosphamide + CAR7-T Cells
fludarabine 30 mg/kg on day -5, -4, and -3; cyclophosphamide 250 mg/kg on day -5, -4, and -3; CAR7-T Cells on day 0.

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
Incidence of Treatment-related Adverse Events
Time Frame: within 2 years after infusion
Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
within 2 years after 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
Overall response rate(ORR) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
Time Frame: within 2 years after infusion
ORR will be assessed from CAR T cell infusion to death or last follow-up (censored).
within 2 years after infusion
Complete response rate(CRR) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
Time Frame: within 2 years after infusion
CRR will be assessed from CAR T cell infusion to death or last follow-up (censored).
within 2 years after infusion
Progress-free survival(PFS) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
Time Frame: within 2 years after infusion
PFS will be assessed from CAR T cell infusion to death or last follow-up (censored).
within 2 years after infusion
Duration of Response(DOR) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
Time Frame: within 2 years after infusion
DOR will be assessed from CAR T cell infusion to death or last follow-up (censored).
within 2 years after infusion
Overall survival(OS) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
Time Frame: within 2 years after infusion
OS will be assessed from CAR T cell infusion to death or last follow-up (censored).
within 2 years after infusion

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
In vivo expansion and survival of CAR7-T cells
Time Frame: within 2 years after infusion
Quantity of CAR copies in bone marrow and peripheral blood will be determined by using quantitative polymerase chain reaction.
within 2 years after 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.
Wuhan Union Hospital, China

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Beijing GoBroad Hospital Management Co.,Ltd
Shanghai YaKe Biotechnology Ltd.

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: Heng Mei, Wuhan Union Hospital, China

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 15, 2021

Primary Completion (Anticipated)

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.
April 7, 2023

Study Completion (Anticipated)

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.
April 7, 2024

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).
March 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.
March 29, 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.
March 30, 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.
March 16, 2022

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.
March 1, 2022

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.
March 1, 2022

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.
  • CAR7-T-cells

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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