CAR-pNK Cell Immunotherapy in CD7 Positive Leukemia and Lymphoma

Acute Myeloid Leukemia Clinical Trial

Official title:

Chimeric Antigen Receptor-Modified pNK Cells for CD7 Positive Relapsed or Refractory Leukemia and Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02742727
• Other study ID #: PG-107-002
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: March 31, 2016
• Last updated: December 4, 2016
• Start date: March 2016
• Est. completion date: March 2018

Study information

• Verified date: December 2016
• Source: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
• Contact: Lin Yang, Ph.D.
• Phone: 86-512-65922190
• Email: info[@]persongen.com
• Is FDA regulated: No
• Health authority: China: National Health and Family Planning Commission
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: March 2018
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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. ? Acute myeloid leukemia, previously identified as CD7+ ? Precursor T lymphoblast 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

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).

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Angioimmunoblastic T-cell Lymphoma
• Enteropathy-Associated T-Cell Lymphoma
• Enteropathy-type Intestinal T-cell Lymphoma
• Extranodal NK/T-cell Lymphoma, Nasal Type
• Hepatosplenic T-cell Lymphoma
• Intestinal Diseases
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid, Acute
• Leukemia, Prolymphocytic
• Leukemia, Prolymphocytic, T-Cell
• Lymphoma
• Lymphoma, Extranodal NK-T-Cell
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T-cell Lymphoma, NOS
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• T-cell Large Granular Lymphocytic Leukemia
• T-cell Prolymphocytic Leukemia

Intervention

Biological:
• anti-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.

Locations

Country	Name	City	State
China	PersonGen BioTherapeutics (Suzhou) Co., Ltd.	Suzhou	Jiangsu

Sponsors (3)

Lead Sponsor	Collaborator
PersonGen BioTherapeutics (Suzhou) Co., Ltd.	Hefei Binhu Hospital, The First People's Hospital of Hefei

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events attributed to the administration of the anti-CD7 CAR-pNK cells	Determine the toxicity profile of the CD7 targeted CAR-pNK cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.	2 years	Yes
Secondary	Clinical response to CD7 CAR-pNK cell infusions	Patients with measurable disease will be assessed for the response of their disease to CD7 CAR-pNK cell treatment.	Safety follow-up is 100 days from last CAR-pNK infusion	No
Secondary	Determine the existence of CD7-CAR-pNK in vivo		1 year	Yes