Clinical trial NCT02742727: CAR-pNK Cell Immunotherapy in CD7 Positive Leukemia and Lymphoma
Official title: Chimeric Antigen Receptor-Modified pNK Cells for CD7 Positive Relapsed or Refractory Leukemia and Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
T-cell Prolymphocytic Leukemia
T-cell Large Granular Lymphocytic Leukemia
Peripheral T-cell Lymphoma, NOS
Angioimmunoblastic T-cell Lymphoma
Extranodal NK/T-cell Lymphoma, Nasal Type
Enteropathy-type Intestinal T-cell Lymphoma
Hepatosplenic T-cell Lymphoma
Lead sponsor: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: The First People's Hospital of Hefei
name: Hefei Binhu Hospital
First posted: 2016-04-19
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Adverse events attributed to the administration of the anti-CD7 CAR-pNK cells
timeFrame: 2 years
Secondary outcomes:
measure: Clinical response to CD7 CAR-pNK cell infusions
timeFrame: Safety follow-up is 100 days from last CAR-pNK infusion
measure: Determine the existence of CD7-CAR-pNK in vivo
timeFrame: 1 year
Other outcomes:
Locations:
city: Suzhou
country: China
facility: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
state: Jiangsu
Study officials:
affiliation: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
name: Lin Yang, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Del Zotto G, Marcenaro E, Vacca P, Sivori S, Pende D, Della Chiesa M, Moretta F, Ingegnere T, Mingari MC, Moretta A, Moretta L. Markers and function of human NK cells in normal and pathological conditions. Cytometry B Clin Cytom. 2017 Mar;92(2):100-114. doi: 10.1002/cyto.b.21508. Epub 2017 Feb 12.