Acute Myeloid Leukemia, Angioimmunoblastic T-cell Lymphoma, Enteropathy-type Intestinal T-cell Lymphoma, Extranodal NK/T-cell Lymphoma, Nasal Type, Hepatosplenic T-cell Lymphoma, Peripheral T-cell Lymphoma, NOS, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, T-cell Large Granular Lymphocytic Leukemia, T-cell Prolymphocytic Leukemia
Conditions
Brief summary
The purpose of this study is to evaluate the safety and effectiveness of CAR-pNK cell immunotherapy in patients with CD7 positive relapsed or refractory Leukemia and Lymphoma.
Interventions
BIOLOGICALanti-CD7 CAR-pNK cells
The allogeneic NK cells (NK-92 cell line for clinical use) are engineered to contain anti-CD7 attached to TCRzeta, CD28 and 4-1BB signaling domains. These modified cells are called chimeric antigen receptor NK cells with specificity for CD7.
Sponsors
The First People's Hospital of Hefei
Hefei Binhu Hospital
PersonGen BioTherapeutics (Suzhou) Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Male and female subjects with CD7+ malignancies in patients with no available curative treatment options who have limited prognosis (several months to \< 2 year survival) with currently available therapies will be enrolled: 1. Eligible diseases: CD7 positive relapsed or refractory Leukemia and Lymphoma. ￚ Acute myeloid leukemia, previously identified as CD7+ ￚ Precursor T lymphoblast leukemia/lymphoma ￚ T-cell prolymphocytic leukemia ￚ T-cell large granular lymphocytic leukemia ￚ Peripheral T-cell lymphoma, NOS ￚ Angioimmunoblastic T-cell lymphoma ￚ Extranodal NK/T-cell lymphoma, nasal type ￚ Enteropathy-type intestinal T-cell lymphoma ￚ Hepatosplenic T-cell lymphoma 2. Patients 18 years of age or older, and must have a life expectancy \> 12 weeks. 3. CD7 is expressed in malignancy tissues by immuno-histochemical (IHC) or Flow cytometry. 4. Assessable disease as measured by laboratory and bone marrow examinations. 5. Eastern cooperative oncology group (ECOG) performance status of 0-2 or karnofsky performance status (KPS) score is higher than 60. 6. Females of child-bearing potential must have a negative pregnancy test and all subjects must agree to use an effective method of contraception for up to two weeks after the last infusion of CAR-pNK cells. 7. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: serum creatinine ≤ 2.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal, serum total bilirubin ≤ 2.0mg/dL. These tests must be conducted within 7 days prior to registration. 8. Ability to give informed consent.
Exclusion criteria
1. Patients with symptomatic central nervous system (CNS) involvement. 2. Pregnant or nursing women may not participate. 3. Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. 4. Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders. 5. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary. 6. Previously treatment with any gene therapy products. 7. The existence of unstable or active ulcers or gastrointestinal bleeding. 8. Patients with a history of organ transplantation or are waiting for organ transplantation. 9. Patients need anticoagulant therapy (such as warfarin or heparin). 10. Patients need long-term antiplatelet therapy (aspirin at a dose \> 300mg/d; clopidogrel at a dose \> 75mg/d).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events attributed to the administration of the anti-CD7 CAR-pNK cells | 2 years | Determine the toxicity profile of the CD7 targeted CAR-pNK cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical response to CD7 CAR-pNK cell infusions | Safety follow-up is 100 days from last CAR-pNK infusion | Patients with measurable disease will be assessed for the response of their disease to CD7 CAR-pNK cell treatment. |
| Determine the existence of CD7-CAR-pNK in vivo | 1 year | — |
Countries
China
Contacts
Primary ContactLin Yang, Ph.D.
Outcome results
None listed