A Study of Anti-CD7 CAR-T Cells in Pediatric and Young Adult Patients With Relapse and Refractory T-ALL/ T-LBL

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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T-cell Acute Lymphoblastic Leukemia, T-lymphoblastic Lymphoma

Intervention / Treatment
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* Biological: Target CD7 CAR-T cells


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Target CD7 CAR-T cells<br>Three dose levels will be evaluated. The CAR-T cells will be administered with Cytoxan and fludarabine. | Biological: Target CD7 CAR-T cells<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | up to 4 weeks after target CD7 CAR-T cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 4 weeks, 12 weeks, 24 weeks after target CD7 CAR-T cells infusion | 
| Progression-free survival (PFS) | PFS determined from patient notes at 24 weeks following target CD7 CAR-T cells infusion. | 24 weeks after target CD7 CAR-T cells infusion | 
| Overall survival (OS) | OS determined from patient notes at 24 weeks. | 24 weeks after target CD7 CAR-T cells infusion | 
| Duration of remission (DOR) | DOR determined from patient notes at 24 weeks. | 24 weeks after target CD7 CAR-T cells infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR-T, CD7, T-ALL/LBL