Back to resultsA Study of Anti-CD7 CAR-T Cells in Pediatric and Young Adult Patients With Relapse and Refractory T-ALL/ T-LBL
Primary Purpose
T-cell Acute Lymphoblastic Leukemia, T-lymphoblastic Lymphoma
Status
Withdrawn
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
Target CD7 CAR-T cells
Sponsored by
About this trial
This is an interventional treatment trial for T-cell Acute Lymphoblastic Leukemia focused on measuring CAR-T, CD7, T-ALL/LBL
Eligibility Criteria
Inclusion Criteria:
- 2 to 25 years
- Diagnosed with relapsed and refractory CD7 + T cell acute lymphocytic leukemia (T-ALL) or relapsed and refractory CD7 + T lymphoblastic lymphoma (T-LBL)
- Quantifiable tumor burden
- Eastern cooperative oncology group (ECOG) performance status of 0 to 1
- Life expectancy ≥12 weeks
Adequate organ function defined as:
- Serum ALT/AST ≤2.5 ULN
- Creatinine clearance (as estimated by Cockcroft Gault) ≥60 mL/min
- PT and APTT≤1.5 ULN
- Total bilirubin ≤1.5 ULN
- Cardiac ejection fraction ≥45%
- No clinically significant ECG findings
- Baseline oxygen saturation >90% on room air
- Recovered from acute toxic effects of prior chemotherapy ≥one week before entering this study
- Agreement to use of medical-approved-contraception during the period of trial and in 1 year after cell transfusion therapy
- Signed informed consent form
Exclusion Criteria:
- Diagnosis of other malignancy (except non-melanoma and cervical carcinoma in situ, bladder cancer, breast cancer that have a disease-free survival of more than 5 years)
- Severe mental disorders
- History of hereditary diseases, including but not limited to: Fanconi anemia, Shut-Dai syndrome, Costman syndrome or any other known bone marrow failure syndrome
- Grade 2-4 acute graft-versus-host disease (GVHD) (Glucksberg criteria) or extensive chronic GVHD (Seattle criteria)
- Grade III-IV heart failure or myocardial infarction, angioplasty or stent placement, unstable angina pectoris, or other clinically prominent heart disease within one year before enrollment
- History or presence of CNS disorder, including but not limited to: seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
- Positive for any of the following etiological tests: HIV, HBV, HCV, TPPA
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled
- Severe allergies
- History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
- History or diagnosis of pulmonary fibrosis
- Participation in other clinical trials ≤4 weeks prior to enrollment
- Concomitant disease that require systemic steroids or other immune suppressive therapy during the study period in researcher's judgement
- Patients who are contraindicated to cyclophosphamide, fludarabine
- Allogeneic cell therapy (such as donor lymphocyte infusion, DLI) ≤6 weeks prior to enrollment
- Poor adherence due to physical, family, social, geographic, and other factors, who cannot follow the research plan and follow-up plan
- Pregnant and lactating women
- Any other conditions that researcher think it is inappropriate for the subject to anticipate the trial
Sites / Locations
- 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Target CD7 CAR-T cells
Arm Description
Three dose levels will be evaluated. The CAR-T cells will be administered with Cytoxan and fludarabine.
Outcomes
Primary Outcome Measures
Number of patients with dose-limiting toxicity
Dose-limiting toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE v5.0) at 4 weeks following target CD7 CAR-T cells infusion
Secondary Outcome Measures
Overall response rate (ORR)
ORR of patients, determined by National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology: Acute Lymphoblastic Leukemia (2016.V2) for T-ALL response rate and Lugano 2014 for T-LBL response rate.
Progression-free survival (PFS)
PFS determined from patient notes at 24 weeks following target CD7 CAR-T cells infusion.
Overall survival (OS)
OS determined from patient notes at 24 weeks.
Duration of remission (DOR)
DOR determined from patient notes at 24 weeks.
Full Information
NCT ID
NCT04860817
First Posted
April 22, 2021
Last Updated
November 23, 2022
Sponsor
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
1. Study Identification
Unique Protocol Identification Number
NCT04860817
Brief Title
A Study of Anti-CD7 CAR-T Cells in Pediatric and Young Adult Patients With Relapse and Refractory T-ALL/ T-LBL
Official Title
Investigating the Safety and Efficacy of Anti-CD7 CAR-T Cell Immunotherapy in Patients With Relapse and Refractory T-cell Acute Lymphoblastic Leukemia or T Lymphoblastic Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Withdrawn
Why Stopped
No proper participant is found.
Study Start Date
December 1, 2021 (Anticipated)
Primary Completion Date
April 30, 2023 (Anticipated)
Study Completion Date
November 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
T cells are a type of immune cell. Like other cells of the body, T Cells can develop cancer. T cell cancers mainly include T cell leukaemia and T cell lymphoma, both of which have a relatively poor prognosis. Currently, patients with relapsed/refractory type (the name given to cancer that reappears or grows again after a period of no changes or signs of cancer) of this leukaemia or lymphoma have limited choices for treatment. CAR-T cells are immune cells that are engineered to target specific cell markers. For example, CAR-T cells targeting the marker CD19 have shown great effectiveness in the treatment of B cell tumors that carry this marker. Here investigators construct a new universal CAR-T design targeting CD7 which is found on the cells of relapsed/refractory type T cell leukaemia and lymphoma and hope to test its safety and efficiency in the treatment of relapsed/refractory type T cell leukaemia and lymphoma.
Detailed Description
Who can participate? Patients diagnosed with relapsed/refractory T cell leukaemia or lymphoma. Both genders, aged 2-25 years old.
What does the study involve? Enrolled participants are randomly chosen to receive one of three different dose levels of CAR-T cells.
Dose level one: 0.6×10^7 cells/kg;
Dose level two: 1×10^7 cells/kg;
Dose level three: 1.5×10^7 cells/kg. Before CAR-T infusion, all participants will receive a preconditioning therapy including several chemotherapy agents or other interventions that are required to help the effect of the CAR-T cells. After completion of preconditioning therapy, infusion of the CAR-T cells via a tube into the vein needs to start within 1 week. Participants will receive one infusion of CAR-T cells which will take between 15 and 30 mins. All participants will have a blood test before infusion and at 4, 7, 10 and 14 days following infusion to measure their response to the treatment and some further tests will be required in some participants.
What are the possible benefits and risks of participating? The universal CAR-T cells targeting CD7 may lead to durable disease control and long term survival. The main risks of participating include cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS).
Where is the study run from? Haematology department of 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China (China).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
T-cell Acute Lymphoblastic Leukemia, T-lymphoblastic Lymphoma
Keywords
CAR-T, CD7, T-ALL/LBL
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Target CD7 CAR-T cells
Arm Type
Experimental
Arm Description
Three dose levels will be evaluated. The CAR-T cells will be administered with Cytoxan and fludarabine.
Intervention Type
Biological
Intervention Name(s)
Target CD7 CAR-T cells
Intervention Description
Enrolled participants are allocated to one of three different dose levels of target CD7 CAR-T cells. The infusion dose of CAR-T cells will start at low dose and then rise to higher dose after completion of low dose group.
Dose level one: 0.6×10^7 cells/kg;
Dose level two: 1×10^7 cells/kg;
Dose level three: 1.5×10^7 cells/kg. Before CAR-T infusion, all participants will receive a preconditioning therapy suggested as: Fludarabine 30 mg/m^2×6d, Cyclophosphamide 300 mg/m^2×6d or Cyclophosphamide 600 mg/m^2×6d. After completion of preconditioning therapy, infusion of CAR-T cells needs to start within 1 week. Participants will receive one infusion of CAR-T cells which will take between 15 and 30 mins.
Primary Outcome Measure Information:
Title
Number of patients with dose-limiting toxicity
Description
Dose-limiting toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE v5.0) at 4 weeks following target CD7 CAR-T cells infusion
Time Frame
up to 4 weeks after target CD7 CAR-T cells infusion
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
ORR of patients, determined by National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology: Acute Lymphoblastic Leukemia (2016.V2) for T-ALL response rate and Lugano 2014 for T-LBL response rate.
Time Frame
4 weeks, 12 weeks, 24 weeks after target CD7 CAR-T cells infusion
Title
Progression-free survival (PFS)
Description
PFS determined from patient notes at 24 weeks following target CD7 CAR-T cells infusion.
Time Frame
24 weeks after target CD7 CAR-T cells infusion
Title
Overall survival (OS)
Description
OS determined from patient notes at 24 weeks.
Time Frame
24 weeks after target CD7 CAR-T cells infusion
Title
Duration of remission (DOR)
Description
DOR determined from patient notes at 24 weeks.
Time Frame
24 weeks after target CD7 CAR-T cells infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
2 to 25 years
Diagnosed with relapsed and refractory CD7 + T cell acute lymphocytic leukemia (T-ALL) or relapsed and refractory CD7 + T lymphoblastic lymphoma (T-LBL)
Quantifiable tumor burden
Eastern cooperative oncology group (ECOG) performance status of 0 to 1
Life expectancy ≥12 weeks
Adequate organ function defined as:
Serum ALT/AST ≤2.5 ULN
Creatinine clearance (as estimated by Cockcroft Gault) ≥60 mL/min
PT and APTT≤1.5 ULN
Total bilirubin ≤1.5 ULN
Cardiac ejection fraction ≥45%
No clinically significant ECG findings
Baseline oxygen saturation >90% on room air
Recovered from acute toxic effects of prior chemotherapy ≥one week before entering this study
Agreement to use of medical-approved-contraception during the period of trial and in 1 year after cell transfusion therapy
Signed informed consent form
Exclusion Criteria:
Diagnosis of other malignancy (except non-melanoma and cervical carcinoma in situ, bladder cancer, breast cancer that have a disease-free survival of more than 5 years)
Severe mental disorders
History of hereditary diseases, including but not limited to: Fanconi anemia, Shut-Dai syndrome, Costman syndrome or any other known bone marrow failure syndrome
Grade 2-4 acute graft-versus-host disease (GVHD) (Glucksberg criteria) or extensive chronic GVHD (Seattle criteria)
Grade III-IV heart failure or myocardial infarction, angioplasty or stent placement, unstable angina pectoris, or other clinically prominent heart disease within one year before enrollment
History or presence of CNS disorder, including but not limited to: seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
Positive for any of the following etiological tests: HIV, HBV, HCV, TPPA
Presence of fungal, bacterial, viral, or other infection that is uncontrolled
Severe allergies
History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
History or diagnosis of pulmonary fibrosis
Participation in other clinical trials ≤4 weeks prior to enrollment
Concomitant disease that require systemic steroids or other immune suppressive therapy during the study period in researcher's judgement
Patients who are contraindicated to cyclophosphamide, fludarabine
Allogeneic cell therapy (such as donor lymphocyte infusion, DLI) ≤6 weeks prior to enrollment
Poor adherence due to physical, family, social, geographic, and other factors, who cannot follow the research plan and follow-up plan
Pregnant and lactating women
Any other conditions that researcher think it is inappropriate for the subject to anticipate the trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sanbin Wang, Doctor
Organizational Affiliation
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Official's Role
Principal Investigator
Facility Information:
Facility Name
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
City
Kunming
State/Province
Yunnan
ZIP/Postal Code
650100 P.R.China
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of Anti-CD7 CAR-T Cells in Pediatric and Young Adult Patients With Relapse and Refractory T-ALL/ T-LBL
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