Anti-CD7 U-CAR-T Cell Therapy for T/NK Cell Hematologic Malignancies

Study Overview
=================
Brief Summary
-----------------
The prognosis of patients with relapsed and/or refractory T-cell hematologic malignancies is poor due to lacking sufficient treatment.Anti-CD(cluster of differentiation antigen)19 CAR(chimeric antigen receptor)-T cell therapies are efficient for patients with B-cell hematologic malignancies. As for T-cell hematologic malignancies, CD7 is a promising target expressed on most malignant T cells. The outcome of CD-7 CAR-T cell therapy pre-clinical experiments is cheerful.however, how to select the functional T cells from the malignant T cells is a challenge. In addition to this, auto-CAR-T cell therapy is not affordable for the majority of patients. Using T cells aphesis from healthy donors edited to avoid rejection of the host as the material of anti-CD7 universal CAR-T cells could be accessible and affordable, which is adapted for patients with CD7+ relapsed and/or refractory T/NK-cell hematologic malignancies.

Official Title
-----------------
Anti-CD7 Universal CAR-T Cells for CD7+ T/NK Cell Hematologic Malignancies: a Multi-center, Uncontrolled Trial

Conditions
-----------------
T-cell Leukemia, T-cell Lymphoma

Intervention / Treatment
-----------------
* Biological: CD7 UCAR-T cells
* Drug: Fludarabine
* Drug: Cytoxan
* Drug: Melphalan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Diagnosis of recurrent T-cell acute lymphoblastic leukemia (T-ALL), T-cell acute lymphoblastic lymphoma (T-LLy), or T-non-Hodgkin lymphoma (T-NHL, including Angioimmunoblastic T-cell lymphoma (AITL), Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), Peripheral T-cell lymphoma (PTCL) NOS, Anaplastic large cell lymphoma (ALCL), Adult T-cell leukemia/lymphoma, T cell prolymphocytic leukemia with symptomatic disease, Extranodal NK/T cell lymphoma, Mycosis fungoides/ Sezary Syndrome Stage IIB or higher)) 2. CD7-positive tumor (≥20% CD7 positive blasts by flow cytometry or immunohistochemistry (tissue)） 3. Hgb ≥ 7.0 (can be transfused) 4. Life expectancy greater than 12 weeks 5. Informed consent explained to, understood by and signed by the patient/guardian. Patient/guardian is given a copy of informed consent. Exclusion Criteria: Pregnant or lactating. Tumor in a location where enlargement could cause airway obstruction (per investigator discretion). Active infection with HIV or HTLV. Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6. Any of the following cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF (left ventricular shortening fraction)<30% or LVEF(left ventricular ejection fraction)<50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA(New York Heart Association) III or IV (Confirmation of absence of these conditions on echocardiogram within 12 months of treatment). CNS abnormalities: Presence of CNS(central nervous system)-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF(cerebrospinal fluid) with ≥ 5 WBC( white blood cell)s per mm3 (unless negative by the Steinherz/Bleyer algorithm); Presence of any CNS disorder such as an uncontrolled seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anti-CD7 UCAR-T cells<br>After preconditioning with chemotherapy ( Fludarabine, Cytoxan and/or Melphalan), the dosage of anti-CD7 UCAR-T cells between 1 and 5 ×10^7 cells/Kg will be evaluated | Biological: CD7 UCAR-T cells<br>* Dose range:1 to 5 ×10^7 cells/Kg, Dose level one: 1×10^7 cells/Kg, Dose level two: 3×10^7 cells/Kg, Dose level three:5 ×10^7 cells/Kg<br>Drug: Fludarabine<br>* 30mg/m^2 per day for 6 days<br>Drug: Cytoxan<br>* 600mg/m^2 per day for 2 to 6 days determined by tumor burden at baseline<br>Drug: Melphalan<br>* 50 to 70 mg/m^2 in total for 1 or 2 days, whether to use determined by tumor burden at baseline<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the anti-tumor efficiency of anti-CD7 UCAR-T cells | ratio of bone marrow blast cells and/or the measurable lesion size and standralized uptake value | 4 weeks after infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the long-term efficiency of anti-CD7 UCAR-T cells | ratio of bone marrow blast cells and/or the measurable lesion size and standralized uptake value | 3 and 6 months after infusion |