CD7 CAR-T Cell Treatment of Relapsed/Refractory CD7+ T -Acute Lymphoblastic Leukemia/ Lymphoma

Study Overview
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Brief Summary
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This is a phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of CD7 CAR-T cells in patients with relapsed and/or refractory, high risk hematologic malignancies.

Detailed Description
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T-acute lymphoblast leukemia (T-ALL) accounts for 15-20% of all ALL cases. It is a neoplastic lymphoid leukemia characterized by the proliferation of immature precursor T cells. T-ALL is a highly aggressive tumor. Adults need intensive chemotherapy, and the cure rate is <50%, even with stem cell transplantation. The prognosis is also very poor. The combined chemotherapy has significantly improved the prognosis of T-acute lymphoblast leukemia/lymphoma. However, once the disease appears to be relapsed/refractory, there is limited treatment options, and the overall prognosis is extremely poor. Therefore, exploring safe and effective treatments is a critical unmet medical need. Since 95% of T-ALLs express CD7, this might provide an effective targeting approach for the vast majority of T-ALL cases.

Official Title
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CD7 CAR-T Cell Treatment of Relapsed/Refractory CD7+ T -Acute Lymphoblastic Leukemia/ Lymphoma

Conditions
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Relapsed/Refractory, High Risk Hematologic Malignancies, T-ALL/Lymphoma

Intervention / Treatment
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* Biological: CD7CAR T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Signed written informed consent; Patients volunteer to participate in the clinical trial; 2. Diagnosis is mainly based on the World Health Organization (WHO) 2008; 3. Complete remission cannot be achieved after induction therapy; recurrence occurs after completion remission; the burden of leukemic blasts in the peripheral blood or bone marrow is greater than 5%; 4. Leukemic blast cells express CD7 (CD7 positive by flow cytometry or immunohistochemistry ≥70%); 5. The expected survival period is greater than 12 weeks; 6. ECOG score ≤2; 7. Age 2-60 years old; 8. HGB≥70g/L (can be transfused); 9. Total bilirubin does not exceed 3 times the upper limit of normal value, and AST and ALT do not exceed 5 times the upper limit of normal value. Exclusion Criteria: 1. Patients declining to consent for treatment 2. Prior solid organ transplantation 3. One of the following cardiac issues: atrial fibrillation; myocardial infarction within the past 12 months; prolonged QT syndrome or secondary QT prolongation; clinically significant pericardial effusion; cardiac insufficiency NYHA (New York Heart Association) III or IV; 4. History of severe pulmonary dysfunction diseases; 5. Severe infection or persistent infection cannot be effectively controlled; 6. Severe autoimmune disease or congenital immunodeficiency; 7. Active hepatitis; 8. Human immunodeficiency virus (HIV) infection; 9. Clinically significant viral infections, or uncontrollable viral reactivation, including EBV (Epstein-Barr virus).

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 60 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: Sequential Assignment
Interventional Model Description: CD7 CAR T cells are used to treat patients. Patient will be administered either fresh or thawed CAR T cells by IV injection after receiving lymphodepleting chemotherapy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD7 CAR T cells<br>Dose escalation phase: CD7 CAR T cells will be transduced with a lentiviral vector to express a CD7 CARs. with an escalation approach, 1 e6 to 7 e6 CAR-T cells/kg | Biological: CD7CAR T cells<br>* CD7 CAR T cells are used to treat patients. Patient will be administered either fresh or thawed CAR T cells by IV injection after receiving lymphodepleting chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number and incidence of adverse events after CD7 CAR infusion. | Evaluation all possible adverse reactions, including the number, incidence, and severity of symptoms such as cytokine release syndromes and neurotoxicity within 3 months after CAR infusion | Up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease response to CD7 CAR T cells | The disease response to CD7 CAR T cells is evaluated by bone marrow biopsy and aspirate within 1 years after CAR infusion. The proportion of subjects receiving CD7 CAR T infusion to 1) morphological remission (blasts <5%): 2) flow cytometry analysis was blast negative, and 3) molecular biological remission (if applicable). | Up to 1 year | 
| Evaluation of curative effects | Evaluation of curative effects within 1 year including 1)completion remission (CR), 2) complete remission with incomplete recovery of blood cells (CRi), 3) minimal residual disease positive (MRD+), 4)minimal residual disease negative (MRD-), and 4) disease recurrence or progression | Up to 1 year | 
| Overall survival | Overall survival {1 year after CAR infusion] . The time from the start of CD7 CAR T injection to death is determined as the overall survival | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD7, CD7CAR, leukemia, acute lymphoblastic leukemia/lymphoma, hematologic malignancies