T-Cell Lymphocytic LeukemiaPhase 1NCT04823091
Anti-CD7 CAR-Engineered T Cells for T Lymphoid Malignancies Malignancies
A Phase 1 study testing Fludarabine + Cyclophosphamide + CAR7-T Cells in people with T-Cell Lymphocytic Leukemia and T-Cell Chronic Lymphocytic Leukemia, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 14 to 70 years
- Conditions the study is for
- T-Cell Lymphocytic Leukemia, T-Cell Chronic Lymphocytic Leukemia, T Cell Non-Hodgkin Lymphoma
- What is being tested?
- Fludarabine + Cyclophosphamide + CAR7-T Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteChina
- Study dates
- 15 Apr 2021to 7 Apr 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Union Hospital, Huazhong University of Science and Technology
Wuhan, Hubei, 430022
Heng Mei, M.D., Ph.D, hmei@hust.edu.cn
Yinqiang Zhang, 15007101371, zyq_107@126.com
About this study
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
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.
Read the 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
- Being tested
- Fludarabine + Cyclophosphamide + CAR7-T Cells
- Medical subject headings
- Leukemia, T-Cell, Leukemia, Prolymphocytic, T-Cell, Lymphoma, T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fludarabine + Cyclophosphamide + CAR7-T CellsDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Fludarabine + Cyclophosphamide + anti-CD7 CAR-T Cells | Experimental | 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. Receives: Drug: Fludarabine + Cyclophosphamide + CAR7-T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: within 2 years after infusion
Secondary outcomes (5)
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).
Measured: within 2 years after infusion
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).
Measured: within 2 years after infusion
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).
Measured: within 2 years after infusion
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).
Measured: within 2 years after infusion
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).
Measured: within 2 years after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2021
- Study start15 Apr 2021
- Primary completion7 Apr 2023 (estimated)
- Study completion7 Apr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for T-Cell Lymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing GoBroad Hospital Management Co.,Ltd, Yake Biotechnology Ltd.
- Responsible party
- Principal investigator, MEI HENG, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Investigators
- Heng Mei, Principal investigator, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04823091
- Sponsor's protocol ID
- CAR7-T-cells
- Status last verified
- Mar 2022
- First submitted
- 29 Mar 2021
- Last updated
- 16 Mar 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 28539325
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04823091
- Acronym / sponsor ID
- CAR7-T-cells
- Conditions
- T-Cell Lymphocytic Leukemia, T-Cell Chronic Lymphocytic Leukemia, T Cell Non-Hodgkin Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyUniversity, hospital or other
- Collaborators
- Beijing GoBroad Hospital Management Co.,Ltd, Yake Biotechnology Ltd.
- Study start
- 15 Apr 2021 (actual)
- Primary completion
- 7 Apr 2023 (estimated)
- Study completion
- 7 Apr 2024 (estimated)
- First posted
- 30 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fludarabine + Cyclophosphamide + anti-CD7 CAR-T Cells | Experimental | Drug: Fludarabine + Cyclophosphamide + CAR7-T CellsPatients 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. |
Who may qualify
- Ages
- 14 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (15 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fludarabine + Cyclophosphamide + CAR7-T Cellsfludarabine 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. | Drug | Fludarabine + Cyclophosphamide + anti-CD7 CAR-T Cells |
Primary outcome
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).
5 secondary outcomes
Overall response rate(ORR) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
Time frame: 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
Progress-free survival(PFS) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
Time frame: 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
Overall survival(OS) of administering CAR7-T cells in Relapsed/Refractory CD7+ T-cell hematological malignancies.
Time frame: within 2 years after infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2022.
- Background: PubMed 28539325Gomes-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heng Mei principal investigator
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fludarabine + Cyclophosphamide + CAR7-T Cells in people with T-Cell Lymphocytic Leukemia and T-Cell Chronic Lymphocytic Leukemia, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Heng Mei (027-8572600, hmei@hust.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-related Adverse Events (time frame: within 2 years after infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04823091, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2022.