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

Primary Purpose

T-Cell Lymphocytic Leukemia, T-Cell Chronic Lymphocytic Leukemia, T Cell Non-Hodgkin Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Fludarabine + Cyclophosphamide + CAR7-T Cells
Sponsored by
Wuhan Union Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for T-Cell Lymphocytic Leukemia

Eligibility Criteria

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

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.

Sites / Locations

  • Union Hospital, Huazhong University of Science and TechnologyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fludarabine + Cyclophosphamide + anti-CD7 CAR-T Cells

Arm Description

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.

Outcomes

Primary Outcome Measures

Incidence of Treatment-related Adverse Events
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).

Secondary Outcome Measures

Overall response rate(ORR) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
ORR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Complete response rate(CRR) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
CRR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Progress-free survival(PFS) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
PFS will be assessed from CAR T cell infusion to death or last follow-up (censored).
Duration of Response(DOR) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
DOR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Overall survival(OS) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
OS will be assessed from CAR T cell infusion to death or last follow-up (censored).

Full Information

First Posted
March 29, 2021
Last Updated
March 1, 2022
Sponsor
Wuhan Union Hospital, China
Collaborators
Beijing GoBroad Hospital Management Co.,Ltd, Shanghai YaKe Biotechnology Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04823091
Brief Title
Anti-CD7 CAR-Engineered T Cells for T Lymphoid Malignancies Malignancies
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 15, 2021 (Actual)
Primary Completion Date
April 7, 2023 (Anticipated)
Study Completion Date
April 7, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Wuhan Union Hospital, China
Collaborators
Beijing GoBroad Hospital Management Co.,Ltd, Shanghai YaKe Biotechnology Ltd.

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 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
T-Cell Lymphocytic Leukemia, T-Cell Chronic Lymphocytic Leukemia, T Cell Non-Hodgkin Lymphoma

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Fludarabine + Cyclophosphamide + anti-CD7 CAR-T Cells
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fludarabine + Cyclophosphamide + CAR7-T Cells
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of Treatment-related Adverse Events
Description
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).
Time Frame
within 2 years after infusion
Secondary Outcome Measure Information:
Title
Overall response rate(ORR) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
Description
ORR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time Frame
within 2 years after infusion
Title
Complete response rate(CRR) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
Description
CRR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time Frame
within 2 years after infusion
Title
Progress-free survival(PFS) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
Description
PFS will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time Frame
within 2 years after infusion
Title
Duration of Response(DOR) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
Description
DOR will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time Frame
within 2 years after infusion
Title
Overall survival(OS) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
Description
OS will be assessed from CAR T cell infusion to death or last follow-up (censored).
Time Frame
within 2 years after infusion
Other Pre-specified Outcome Measures:
Title
In vivo expansion and survival of CAR7-T cells
Description
Quantity of CAR copies in bone marrow and peripheral blood will be determined by using quantitative polymerase chain reaction.
Time Frame
within 2 years after infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged from 14 to 70 years; Expected survival over 60 days; Eastern Cooperative Oncology Group score 0-2; Diagnosed as T-cell hematologic malignancies (including leukemia and lymphoma) according to WHO2016 criteria; Patients must relapse or be refractory after at least two lines of therapy. 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; Have no fertility requirements or plans for one year since enrollment in this clinical trial; Patient or his or her legal guardian voluntarily participates in and signs an informed consent form. Exclusion Criteria: Complicated with central system leukemia/lymphoma with active intracranial lesions; Existing or preexisting CNS conditions, such as epileptic seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS related autoimmune disease; Symptomatic heart failure or severe arrhythmias; Symptoms of severe respiratory failure; Complicated with other types of malignant tumors; Serum creatinine and/or urea nitrogen ≥ 1.5 times of normal value; Suffer from sepsis or other uncontrollable infections; Intracranial hypertension or brain consciousness disorder; Severe mental disorders; Have received organ transplantation (excluding bone marrow transplantation); Female patients (fertile patients) had positive blood HCG test; Hepatitis (including hepatitis B and C), AIDS and syphilis were screened positive; Patients with graft-versus-host disease (GVHD) or who require immunosuppressant treatment; The absolute value of lymphocytes was too low to manufacture CART cells; Other conditions considered inappropriate by the researcher.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Heng Mei
Phone
027-8572600
Email
hmei@hust.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Chenggong Li
Phone
18868112136
Email
chenggongli@hust.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heng Mei
Organizational Affiliation
Wuhan Union Hospital, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Union Hospital, Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430022
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heng Mei, M.D., Ph.D
Email
hmei@hust.edu.cn
First Name & Middle Initial & Last Name & Degree
Yinqiang Zhang
Phone
15007101371
Email
zyq_107@126.com
First Name & Middle Initial & Last Name & Degree
Heng Mei, M.D., Ph.D

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28539325
Citation
Gomes-Silva D, Srinivasan M, Sharma S, Lee CM, Wagner DL, Davis TH, Rouce RH, Bao G, Brenner MK, Mamonkin M. CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies. Blood. 2017 Jul 20;130(3):285-296. doi: 10.1182/blood-2017-01-761320. Epub 2017 May 24.
Results Reference
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Anti-CD7 CAR-Engineered T Cells for T Lymphoid Malignancies Malignancies

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