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

NCT ID: NCT04823091

Last Updated: 2022-03-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-15
• Study Completion Date: 2024-04-07

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Fludarabine + Cyclophosphamide + CAR7-T Cells

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing GoBroad Hospital Management Co.,Ltd

UNKNOWN

Sponsor Role: collaborator

Yake Biotechnology Ltd.

INDUSTRY

Sponsor Role: collaborator

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

MEI HENG

Proferssor, Cheif Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Heng Mei

Role: PRINCIPAL_INVESTIGATOR

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Locations

Union Hospital, Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status: RECRUITING

Countries

China

Central Contacts

Heng Mei

Role: CONTACT

hmei@hust.edu.cn

027-8572600

Chenggong Li

Role: CONTACT

chenggongli@hust.edu.cn

18868112136

Facility Contacts

Heng Mei, M.D., Ph.D

Role: primary

hmei@hust.edu.cn

Yinqiang Zhang

Role: backup

zyq_107@126.com

15007101371

References

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.

Reference Type: BACKGROUND

PMID: 28539325 (View on PubMed)

Other Identifiers

CAR7-T-cells

Identifier Type: -

Identifier Source: org_study_id